CA1333807C - Process for preparing (trans)-4-phenyl-l-proline derivatives - Google Patents

Process for preparing (trans)-4-phenyl-l-proline derivatives

Info

Publication number: CA1333807C
Authority: CA; Canada
Prior art keywords: proline; benzoyl; trans; lactone; phenyl
Prior art date: 1987-06-15
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.): Expired - Lifetime

Application number

CA000566007A

Other languages

English (en)

French (fr)

Inventor

David R. Kronenthal

Paula L. Kuester

Richard H. Mueller

Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)

ER Squibb and Sons LLC

Original Assignee

ER Squibb and Sons LLC

Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)

1987-06-15

Filing date

1988-05-05

Publication date

1995-01-03

1988-05-05 Application filed by ER Squibb and Sons LLC filed Critical ER Squibb and Sons LLC

1995-01-03 Application granted granted Critical

1995-01-03 Publication of CA1333807C publication Critical patent/CA1333807C/en

2012-01-03 Anticipated expiration legal-status Critical

Status Expired - Lifetime legal-status Critical Current

Links

JHHOFXBPLJDHOR-ZJUUUORDSA-N (2s,4s)-4-phenylpyrrolidin-1-ium-2-carboxylate Chemical class C1N[C@H](C(=O)O)C[C@H]1C1=CC=CC=C1 JHHOFXBPLJDHOR-ZJUUUORDSA-N 0.000 title claims abstract description 12
238000004519 manufacturing process Methods 0.000 title claims description 4
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims abstract description 52
238000000034 method Methods 0.000 claims abstract description 23
-1 proline lactone Chemical class 0.000 claims abstract description 19
VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 claims abstract description 16
150000003147 proline derivatives Chemical class 0.000 claims abstract description 16
229960002429 proline Drugs 0.000 claims abstract description 15
125000003118 aryl group Chemical group 0.000 claims abstract description 11
ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 claims abstract description 9
239000007858 starting material Substances 0.000 claims abstract description 8
239000002841 Lewis acid Substances 0.000 claims abstract description 7
150000007517 lewis acids Chemical class 0.000 claims abstract description 7
125000000217 alkyl group Chemical group 0.000 claims abstract description 5
QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims abstract description 5
125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 claims abstract 2
238000006243 chemical reaction Methods 0.000 claims description 29
150000002596 lactones Chemical class 0.000 claims description 14
239000011541 reaction mixture Substances 0.000 claims description 8
JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 claims description 8
239000007795 chemical reaction product Substances 0.000 claims description 7
239000012038 nucleophile Substances 0.000 claims description 7
239000002585 base Substances 0.000 claims description 6
125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 6
125000003541 2-chlorobenzoyl group Chemical group ClC1=C(C(=O)*)C=CC=C1 0.000 claims description 5
AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 claims description 5
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 5
125000000242 4-chlorobenzoyl group Chemical group ClC1=CC=C(C(=O)*)C=C1 0.000 claims description 4
125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 4
229910052736 halogen Inorganic materials 0.000 claims description 4
150000002367 halogens Chemical class 0.000 claims description 4
125000005441 o-toluyl group Chemical group [H]C1=C([H])C(C(*)=O)=C(C([H])=C1[H])C([H])([H])[H] 0.000 claims description 4
239000003960 organic solvent Substances 0.000 claims description 4
125000003232 p-nitrobenzoyl group Chemical group [N+](=O)([O-])C1=CC=C(C(=O)*)C=C1 0.000 claims description 4
125000005440 p-toluyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1C(*)=O)C([H])([H])[H] 0.000 claims description 4
ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical compound [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 0.000 claims description 4
125000004044 trifluoroacetyl group Chemical group FC(C(=O)*)(F)F 0.000 claims description 4
KXFSUVJPEQYUGN-UHFFFAOYSA-N trimethyl(phenyl)silane Chemical compound C[Si](C)(C)C1=CC=CC=C1 KXFSUVJPEQYUGN-UHFFFAOYSA-N 0.000 claims description 4
239000012298 atmosphere Substances 0.000 claims description 3
150000001555 benzenes Chemical class 0.000 claims description 3
125000005905 mesyloxy group Chemical group 0.000 claims description 3
239000000376 reactant Substances 0.000 claims description 3
239000003054 catalyst Substances 0.000 claims description 2
125000001475 halogen functional group Chemical group 0.000 claims 1
229910052731 fluorine Inorganic materials 0.000 abstract description 4
239000005541 ACE inhibitor Substances 0.000 abstract description 3
ONIBWKKTOPOVIA-BYPYZUCNSA-N L-Proline Chemical compound OC(=O)[C@@H]1CCCN1 ONIBWKKTOPOVIA-BYPYZUCNSA-N 0.000 abstract description 3
229940044094 angiotensin-converting-enzyme inhibitor Drugs 0.000 abstract description 3
PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 abstract description 2
239000011737 fluorine Substances 0.000 abstract description 2
238000003547 Friedel-Crafts alkylation reaction Methods 0.000 abstract 1
125000003710 aryl alkyl group Chemical group 0.000 abstract 1
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 103
235000019439 ethyl acetate Nutrition 0.000 description 35
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 30
239000000243 solution Substances 0.000 description 30
239000000203 mixture Substances 0.000 description 27
XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 26
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 26
IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 24
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 21
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 18
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 18
239000000047 product Substances 0.000 description 18
239000000460 chlorine Substances 0.000 description 17
239000012267 brine Substances 0.000 description 16
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 16
229910052786 argon Inorganic materials 0.000 description 13
239000000284 extract Substances 0.000 description 13
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 12
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 12
DKPFZGUDAPQIHT-UHFFFAOYSA-N butyl acetate Chemical compound CCCCOC(C)=O DKPFZGUDAPQIHT-UHFFFAOYSA-N 0.000 description 12
150000001875 compounds Chemical class 0.000 description 12
239000013078 crystal Substances 0.000 description 12
WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 11
239000010410 layer Substances 0.000 description 11
NJMASXVCJXPDME-CVEARBPZSA-N (2s,4s)-1-benzoyl-4-phenylpyrrolidine-2-carboxylic acid Chemical compound C([C@@H](C[C@H]1C(=O)O)C=2C=CC=CC=2)N1C(=O)C1=CC=CC=C1 NJMASXVCJXPDME-CVEARBPZSA-N 0.000 description 10
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 10
ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 9
239000007787 solid Substances 0.000 description 9
YYROPELSRYBVMQ-UHFFFAOYSA-N 4-toluenesulfonyl chloride Chemical compound CC1=CC=C(S(Cl)(=O)=O)C=C1 YYROPELSRYBVMQ-UHFFFAOYSA-N 0.000 description 8
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 8
239000000706 filtrate Substances 0.000 description 8
238000001914 filtration Methods 0.000 description 8
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 8
238000003756 stirring Methods 0.000 description 8
239000000725 suspension Substances 0.000 description 8
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 7
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 6
239000002253 acid Substances 0.000 description 6
238000013019 agitation Methods 0.000 description 6
KJIFKLIQANRMOU-UHFFFAOYSA-N oxidanium;4-methylbenzenesulfonate Chemical group O.CC1=CC=C(S(O)(=O)=O)C=C1 KJIFKLIQANRMOU-UHFFFAOYSA-N 0.000 description 6
238000010992 reflux Methods 0.000 description 6
238000009835 boiling Methods 0.000 description 5
239000012043 crude product Substances 0.000 description 5
239000012044 organic layer Substances 0.000 description 5
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 5
ZLUIBJGFQFHEPT-QWRGUYRKSA-N (2s,4s)-1-benzoyl-4-methylsulfonyloxypyrrolidine-2-carboxylic acid Chemical compound C1[C@@H](OS(=O)(=O)C)C[C@@H](C(O)=O)N1C(=O)C1=CC=CC=C1 ZLUIBJGFQFHEPT-QWRGUYRKSA-N 0.000 description 4
VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 4
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 4
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 4
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 4
PASDCCFISLVPSO-UHFFFAOYSA-N benzoyl chloride Chemical compound ClC(=O)C1=CC=CC=C1 PASDCCFISLVPSO-UHFFFAOYSA-N 0.000 description 4
239000006227 byproduct Substances 0.000 description 4
229910052801 chlorine Inorganic materials 0.000 description 4
CSJLBAMHHLJAAS-UHFFFAOYSA-N diethylaminosulfur trifluoride Chemical compound CCN(CC)S(F)(F)F CSJLBAMHHLJAAS-UHFFFAOYSA-N 0.000 description 4
239000005457 ice water Substances 0.000 description 4
229910000027 potassium carbonate Inorganic materials 0.000 description 4
239000002002 slurry Substances 0.000 description 4
229910052938 sodium sulfate Inorganic materials 0.000 description 4
235000011152 sodium sulphate Nutrition 0.000 description 4
RFFLAFLAYFXFSW-UHFFFAOYSA-N 1,2-dichlorobenzene Chemical compound ClC1=CC=CC=C1Cl RFFLAFLAYFXFSW-UHFFFAOYSA-N 0.000 description 3
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
239000007864 aqueous solution Substances 0.000 description 3
229910052794 bromium Inorganic materials 0.000 description 3
125000004432 carbon atom Chemical group C* 0.000 description 3
229910052740 iodine Inorganic materials 0.000 description 3
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
229910052757 nitrogen Inorganic materials 0.000 description 3
235000015497 potassium bicarbonate Nutrition 0.000 description 3
229910000028 potassium bicarbonate Inorganic materials 0.000 description 3
239000011736 potassium bicarbonate Substances 0.000 description 3
TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 3
YLJPKSKTKJEACX-ZJUUUORDSA-N (2s,4r)-1-benzoyl-4-hydroxypyrrolidine-2-carboxylic acid Chemical compound C1[C@H](O)C[C@@H](C(O)=O)N1C(=O)C1=CC=CC=C1 YLJPKSKTKJEACX-ZJUUUORDSA-N 0.000 description 2
PMMYEEVYMWASQN-DMTCNVIQSA-N Hydroxyproline Chemical compound O[C@H]1CN[C@H](C(O)=O)C1 PMMYEEVYMWASQN-DMTCNVIQSA-N 0.000 description 2
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 description 2
125000003545 alkoxy group Chemical group 0.000 description 2
238000006480 benzoylation reaction Methods 0.000 description 2
RBHJBMIOOPYDBQ-UHFFFAOYSA-N carbon dioxide;propan-2-one Chemical compound O=C=O.CC(C)=O RBHJBMIOOPYDBQ-UHFFFAOYSA-N 0.000 description 2
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 2
MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 description 2
238000001816 cooling Methods 0.000 description 2
238000000326 densiometry Methods 0.000 description 2
PMMYEEVYMWASQN-UHFFFAOYSA-N dl-hydroxyproline Natural products OC1C[NH2+]C(C([O-])=O)C1 PMMYEEVYMWASQN-UHFFFAOYSA-N 0.000 description 2
239000006260 foam Substances 0.000 description 2
229910052739 hydrogen Inorganic materials 0.000 description 2
229960002591 hydroxyproline Drugs 0.000 description 2
239000007788 liquid Substances 0.000 description 2
229910052943 magnesium sulfate Inorganic materials 0.000 description 2
235000019341 magnesium sulphate Nutrition 0.000 description 2
238000004949 mass spectrometry Methods 0.000 description 2
QEQGWOLBDNOSAD-MNOVXSKESA-N methyl (2s,4r)-1-benzoyl-4-hydroxypyrrolidine-2-carboxylate Chemical compound COC(=O)[C@@H]1C[C@@H](O)CN1C(=O)C1=CC=CC=C1 QEQGWOLBDNOSAD-MNOVXSKESA-N 0.000 description 2
239000012452 mother liquor Substances 0.000 description 2
235000015320 potassium carbonate Nutrition 0.000 description 2
235000011181 potassium carbonates Nutrition 0.000 description 2
239000000741 silica gel Substances 0.000 description 2
229910002027 silica gel Inorganic materials 0.000 description 2
SQGYOTSLMSWVJD-UHFFFAOYSA-N silver(1+) nitrate Chemical compound [Ag+].[O-]N(=O)=O SQGYOTSLMSWVJD-UHFFFAOYSA-N 0.000 description 2
235000017557 sodium bicarbonate Nutrition 0.000 description 2
229910000030 sodium bicarbonate Inorganic materials 0.000 description 2
239000002904 solvent Substances 0.000 description 2
VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 2
RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 2
HJLFRTVSHWGQMY-UXQCFNEQSA-N (2s,4r)-1-benzoyl-4-hydroxypyrrolidine-2-carboxylic acid;4-methylbenzenesulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1.C1[C@H](O)C[C@@H](C(O)=O)N1C(=O)C1=CC=CC=C1 HJLFRTVSHWGQMY-UXQCFNEQSA-N 0.000 description 1
JHHOFXBPLJDHOR-UWVGGRQHSA-N (2s,4r)-4-phenylpyrrolidin-1-ium-2-carboxylate Chemical compound C1N[C@H](C(=O)O)C[C@@H]1C1=CC=CC=C1 JHHOFXBPLJDHOR-UWVGGRQHSA-N 0.000 description 1
BIDNLKIUORFRQP-XYGFDPSESA-N (2s,4s)-4-cyclohexyl-1-[2-[[(1s)-2-methyl-1-propanoyloxypropoxy]-(4-phenylbutyl)phosphoryl]acetyl]pyrrolidine-2-carboxylic acid Chemical compound C([P@@](=O)(O[C@H](OC(=O)CC)C(C)C)CC(=O)N1[C@@H](C[C@H](C1)C1CCCCC1)C(O)=O)CCCC1=CC=CC=C1 BIDNLKIUORFRQP-XYGFDPSESA-N 0.000 description 1
BHKKSKOHRFHHIN-MRVPVSSYSA-N 1-[[2-[(1R)-1-aminoethyl]-4-chlorophenyl]methyl]-2-sulfanylidene-5H-pyrrolo[3,2-d]pyrimidin-4-one Chemical compound N[C@H](C)C1=C(CN2C(NC(C3=C2C=CN3)=O)=S)C=CC(=C1)Cl BHKKSKOHRFHHIN-MRVPVSSYSA-N 0.000 description 1
ZQXCQTAELHSNAT-UHFFFAOYSA-N 1-chloro-3-nitro-5-(trifluoromethyl)benzene Chemical compound [O-][N+](=O)C1=CC(Cl)=CC(C(F)(F)F)=C1 ZQXCQTAELHSNAT-UHFFFAOYSA-N 0.000 description 1
ONIKNECPXCLUHT-UHFFFAOYSA-N 2-chlorobenzoyl chloride Chemical compound ClC(=O)C1=CC=CC=C1Cl ONIKNECPXCLUHT-UHFFFAOYSA-N 0.000 description 1
AWGBKZRMLNVLAF-UHFFFAOYSA-N 3,5-dibromo-n,2-dihydroxybenzamide Chemical compound ONC(=O)C1=CC(Br)=CC(Br)=C1O AWGBKZRMLNVLAF-UHFFFAOYSA-N 0.000 description 1
ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 1
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
WSNMPAVSZJSIMT-UHFFFAOYSA-N COc1c(C)c2COC(=O)c2c(O)c1CC(O)C1(C)CCC(=O)O1 Chemical compound COc1c(C)c2COC(=O)c2c(O)c1CC(O)C1(C)CCC(=O)O1 WSNMPAVSZJSIMT-UHFFFAOYSA-N 0.000 description 1
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
241000518994 Conta Species 0.000 description 1
229910004373 HOAc Inorganic materials 0.000 description 1
DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
238000012369 In process control Methods 0.000 description 1
239000012359 Methanesulfonyl chloride Substances 0.000 description 1
VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 1
ZMQBBPRAZLACCW-UHFFFAOYSA-N acetic acid;dichloromethane Chemical compound ClCCl.CC(O)=O ZMQBBPRAZLACCW-UHFFFAOYSA-N 0.000 description 1
239000003377 acid catalyst Substances 0.000 description 1
125000004414 alkyl thio group Chemical group 0.000 description 1
238000004458 analytical method Methods 0.000 description 1
239000006286 aqueous extract Substances 0.000 description 1
239000008346 aqueous phase Substances 0.000 description 1
239000012300 argon atmosphere Substances 0.000 description 1
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
125000001589 carboacyl group Chemical group 0.000 description 1
238000002425 crystallisation Methods 0.000 description 1
230000008025 crystallization Effects 0.000 description 1
125000000392 cycloalkenyl group Chemical group 0.000 description 1
125000000753 cycloalkyl group Chemical group 0.000 description 1
238000000354 decomposition reaction Methods 0.000 description 1
239000012067 demethylated product Substances 0.000 description 1
125000004663 dialkyl amino group Chemical group 0.000 description 1
239000006185 dispersion Substances 0.000 description 1
238000004821 distillation Methods 0.000 description 1
238000001035 drying Methods 0.000 description 1
239000003480 eluent Substances 0.000 description 1
230000032050 esterification Effects 0.000 description 1
238000005886 esterification reaction Methods 0.000 description 1
150000002148 esters Chemical class 0.000 description 1
LJQKCYFTNDAAPC-UHFFFAOYSA-N ethanol;ethyl acetate Chemical compound CCO.CCOC(C)=O LJQKCYFTNDAAPC-UHFFFAOYSA-N 0.000 description 1
NLFBCYMMUAKCPC-KQQUZDAGSA-N ethyl (e)-3-[3-amino-2-cyano-1-[(e)-3-ethoxy-3-oxoprop-1-enyl]sulfanyl-3-oxoprop-1-enyl]sulfanylprop-2-enoate Chemical compound CCOC(=O)\C=C\SC(=C(C#N)C(N)=O)S\C=C\C(=O)OCC NLFBCYMMUAKCPC-KQQUZDAGSA-N 0.000 description 1
PQVSTLUFSYVLTO-UHFFFAOYSA-N ethyl n-ethoxycarbonylcarbamate Chemical compound CCOC(=O)NC(=O)OCC PQVSTLUFSYVLTO-UHFFFAOYSA-N 0.000 description 1
238000002474 experimental method Methods 0.000 description 1
238000000605 extraction Methods 0.000 description 1
239000012530 fluid Substances 0.000 description 1
125000001153 fluoro group Chemical group F* 0.000 description 1
229960002490 fosinopril Drugs 0.000 description 1
239000008241 heterogeneous mixture Substances 0.000 description 1
238000004128 high performance liquid chromatography Methods 0.000 description 1
230000007062 hydrolysis Effects 0.000 description 1
238000006460 hydrolysis reaction Methods 0.000 description 1
XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 1
125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
238000010965 in-process control Methods 0.000 description 1
239000000543 intermediate Substances 0.000 description 1
239000011630 iodine Substances 0.000 description 1
GJRQTCIYDGXPES-UHFFFAOYSA-N iso-butyl acetate Natural products CC(C)COC(C)=O GJRQTCIYDGXPES-UHFFFAOYSA-N 0.000 description 1
FGKJLKRYENPLQH-UHFFFAOYSA-M isocaproate Chemical compound CC(C)CCC([O-])=O FGKJLKRYENPLQH-UHFFFAOYSA-M 0.000 description 1
OQAGVSWESNCJJT-UHFFFAOYSA-N isovaleric acid methyl ester Natural products COC(=O)CC(C)C OQAGVSWESNCJJT-UHFFFAOYSA-N 0.000 description 1
GLXDVVHUTZTUQK-UHFFFAOYSA-M lithium hydroxide monohydrate Substances [Li+].O.[OH-] GLXDVVHUTZTUQK-UHFFFAOYSA-M 0.000 description 1
229940040692 lithium hydroxide monohydrate Drugs 0.000 description 1
239000000463 material Substances 0.000 description 1
VNWKTOKETHGBQD-UHFFFAOYSA-N methane Chemical compound C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 1
QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 1
VHQQUQWNCVWPDS-AEFFLSMTSA-N methyl (2s,4r)-1-benzoyl-4-(4-methylphenyl)sulfonyloxypyrrolidine-2-carboxylate Chemical compound C([C@@H](C[C@H]1C(=O)OC)OS(=O)(=O)C=2C=CC(C)=CC=2)N1C(=O)C1=CC=CC=C1 VHQQUQWNCVWPDS-AEFFLSMTSA-N 0.000 description 1
QEQGWOLBDNOSAD-QWRGUYRKSA-N methyl (2s,4s)-1-benzoyl-4-hydroxypyrrolidine-2-carboxylate Chemical compound COC(=O)[C@@H]1C[C@H](O)CN1C(=O)C1=CC=CC=C1 QEQGWOLBDNOSAD-QWRGUYRKSA-N 0.000 description 1
238000002156 mixing Methods 0.000 description 1
230000007935 neutral effect Effects 0.000 description 1
238000010899 nucleation Methods 0.000 description 1
BSCHIACBONPEOB-UHFFFAOYSA-N oxolane;hydrate Chemical compound O.C1CCOC1 BSCHIACBONPEOB-UHFFFAOYSA-N 0.000 description 1
239000012071 phase Substances 0.000 description 1
125000006678 phenoxycarbonyl group Chemical group 0.000 description 1
238000002360 preparation method Methods 0.000 description 1
238000000746 purification Methods 0.000 description 1
239000013557 residual solvent Substances 0.000 description 1
239000000523 sample Substances 0.000 description 1
238000007127 saponification reaction Methods 0.000 description 1
229920006395 saturated elastomer Polymers 0.000 description 1
229910001961 silver nitrate Inorganic materials 0.000 description 1
229910052708 sodium Inorganic materials 0.000 description 1
239000011734 sodium Substances 0.000 description 1
239000001632 sodium acetate Substances 0.000 description 1
235000017281 sodium acetate Nutrition 0.000 description 1
239000011780 sodium chloride Substances 0.000 description 1
238000000527 sonication Methods 0.000 description 1
238000010183 spectrum analysis Methods 0.000 description 1
YBBRCQOCSYXUOC-UHFFFAOYSA-N sulfuryl dichloride Chemical compound ClS(Cl)(=O)=O YBBRCQOCSYXUOC-UHFFFAOYSA-N 0.000 description 1
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
229930192474 thiophene Natural products 0.000 description 1
PMMYEEVYMWASQN-IMJSIDKUSA-N trans-4-Hydroxy-L-proline Natural products O[C@@H]1CN[C@H](C(O)=O)C1 PMMYEEVYMWASQN-IMJSIDKUSA-N 0.000 description 1
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
239000003039 volatile agent Substances 0.000 description 1
238000010792 warming Methods 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/04—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D207/10—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D207/16—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups

Landscapes

Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Pyrrole Compounds (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)

CA000566007A 1987-06-15 1988-05-05 Process for preparing (trans)-4-phenyl-l-proline derivatives Expired - Lifetime CA1333807C (en)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
US6151187A	1987-06-15	1987-06-15
US61,511		1987-06-15

Publications (1)

Publication Number	Publication Date
CA1333807C true CA1333807C (en)	1995-01-03

Family

ID=22036252

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
CA000566007A Expired - Lifetime CA1333807C (en)	1987-06-15	1988-05-05	Process for preparing (trans)-4-phenyl-l-proline derivatives

Country Status (6)

Country	Link
JP (1)	JPH0832677B2 (it)
CA (1)	CA1333807C (it)
DE (1)	DE3820230C2 (it)
FR (1)	FR2616431B1 (it)
GB (1)	GB2205832B (it)
IT (1)	IT1218074B (it)

Families Citing this family (2)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
DK0915088T3 (da)	1997-10-31	2003-01-27	Hoffmann La Roche	D-prolinderivater
US7659305B2 (en)	2002-10-31	2010-02-09	Pfizer Inc.	Therapeutic proline derivatives

Family Cites Families (4)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US4303662A (en) *	1980-11-24	1981-12-01	E. R. Squibb & Sons, Inc.	Carboxyacyl, mercapto and acylmercapto derivatives of heterobicyclo compounds
US4337201A (en) *	1980-12-04	1982-06-29	E. R. Squibb & Sons, Inc.	Phosphinylalkanoyl substituted prolines
US4501901A (en) *	1983-09-19	1985-02-26	E. R. Squibb & Sons, Inc.	Method for making substituted prolines
US4588819A (en) *	1984-11-19	1986-05-13	E. R. Squibb & Sons, Inc.	Process and intermediates for preparing trans-4-substituted-s-prolines

1988
- 1988-05-05 CA CA000566007A patent/CA1333807C/en not_active Expired - Lifetime
- 1988-06-09 GB GB8813659A patent/GB2205832B/en not_active Expired - Lifetime
- 1988-06-13 FR FR888807841A patent/FR2616431B1/fr not_active Expired - Lifetime
- 1988-06-13 IT IT20949/88A patent/IT1218074B/it active
- 1988-06-14 DE DE3820230A patent/DE3820230C2/de not_active Expired - Lifetime
- 1988-06-14 JP JP63146690A patent/JPH0832677B2/ja not_active Expired - Lifetime

Also Published As

Publication number	Publication date
GB2205832A (en)	1988-12-21
IT8820949A0 (it)	1988-06-13
IT1218074B (it)	1990-04-12
FR2616431B1 (fr)	1994-08-12
DE3820230A1 (de)	1988-12-29
GB8813659D0 (en)	1988-07-13
JPH0832677B2 (ja)	1996-03-29
DE3820230C2 (de)	2002-11-07
JPS6416761A (en)	1989-01-20
GB2205832B (en)	1991-07-17
FR2616431A1 (fr)	1988-12-16

Legal Events

Date	Code	Title	Description
2012-01-03	MKEX	Expiry
2023-05-26	MKEX	Expiry	Effective date: 20120103

Publication	Publication Date	Title
US8153801B2 (en)	2012-04-10	Process and intermediates for preparing integrase inhibitors
US4912231A (en)	1990-03-27	Process for preparing (trans)-4-phenyl-L-proline derivatives
SK283894B6 (sk)	2004-04-06	Spôsob výroby 5-[2-etoxy-5-(4-metylpiperazin-1-ylsulfonyl)- fenyl]-1-metyl-3-n-propyl-1,6-dihydro-7H-pyrazolo [4,3-d]pyrimidin-7-ónu
IL197527A (en)	2013-08-29	4-oxo-quinolone derivatives and process and intermediates for preparing integrase inhibitors
ES2336333T3 (es)	2010-04-12	Proceso para preparacion de derivados de tetrazol de azidas de organoaluminio y organoboro.
KR20110041431A (ko)	2011-04-21	결정성 고체 두타스터라이드 및 그의 제조방법
DE69306595T2 (de)	1997-04-03	Regioselektive synthese von 4-chlor-2-thiophencarbonsäure
JPS626718B2 (it)	1987-02-13
CA1333807C (en)	1995-01-03	Process for preparing (trans)-4-phenyl-l-proline derivatives
CA1271769A (en)	1990-07-17	4-alkoxy-3-pyrrolin-2-on-1-yl acetic acid alkyl esters and their production
EP0284076B1 (en)	1994-06-08	Process for preparing (+)-1,2-dihydro-3H-pyrrolo[1,2-a]pyrrole-1-carboxylic acid and related compounds
US20060142595A1 (en)	2006-06-29	Process for preparing 5,6-dihydro-4-(S)-(ethylamino)-6-(S) methyl-4H-thieno[2,3b]thiopyran-2-sulphonamide-7,7-dioxide HCI
JPH04210957A (ja)	1992-08-03	シクロペンテン化合物の製法
US6175009B1 (en)	2001-01-16	Process for the preparation of quinazolinones
RU2032679C1 (ru)	1995-04-10	Производные бензатиазинов
US5532381A (en)	1996-07-02	Process for preparing pyrrolizine derivatives
JPH069553A (ja)	1994-01-18	１−［｜２ｓ｜−メチル−３−メルカプトプロピオニル−ピロリジン−｜２ｓ｜−カルボン酸の製法
JPH08501306A (ja)	1996-02-13	キラルなキノロン誘導体
CN118613470B (zh)	2025-08-15	7,8-二氢-2h-环戊二烯并吡咯并吡嗪酮化合物的合成方法
US4889929A (en)	1989-12-26	Preparation of 1'-ethoxycarbonyl-oxyethyl esters of penicillins
JP4181233B2 (ja)	2008-11-12	ピロリジン−２，４−ジオン誘導体の製法
EP1623975A1 (en)	2006-02-08	Process for producing pyrrolidine derivative
Okada et al.	2001	New method for the synthesis of pyrromethanes
KR930006289B1 (ko)	1993-07-12	디히드로후라논 유도체의 제조방법
Faigl et al.	2003	Efficient methods for optional metalation of 1-(methylphenyl) pyrroles in α or benzylic positions