CA1273352A - Intermediaires utilises dans la preparation d'inhibiteurs de la reductase hmg-coa - Google Patents

Intermediaires utilises dans la preparation d'inhibiteurs de la reductase hmg-coa

Info

Publication number: CA1273352A
Authority: CA; Canada
Prior art keywords: compound; mmol; ethyl; alkyl; bromo
Prior art date: 1984-11-19
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

CA000546907A

Other languages

English (en)

Inventor

Howard E. Morton

Yvan Guindon

Christiane Yoakim

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.)

Merck Frosst Canada and Co

Original Assignee

Merck Frosst Canada and Co

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.)

1984-11-19

Filing date

1987-09-15

Publication date

1990-08-28

1984-11-19 Priority claimed from US06/673,231 external-priority patent/US4611068A/en

1987-09-15 Application filed by Merck Frosst Canada and Co filed Critical Merck Frosst Canada and Co

1987-09-15 Priority to CA000546907A priority Critical patent/CA1273352A/fr

1990-08-28 Application granted granted Critical

1990-08-28 Publication of CA1273352A publication Critical patent/CA1273352A/fr

2007-08-28 Anticipated expiration legal-status Critical

Status Expired - Lifetime legal-status Critical Current

Links

238000002360 preparation method Methods 0.000 title abstract description 13
229940121710 HMGCoA reductase inhibitor Drugs 0.000 title abstract 2
239000002471 hydroxymethylglutaryl coenzyme A reductase inhibitor Substances 0.000 title abstract 2
239000000543 intermediate Substances 0.000 title abstract 2
229940096701 plain lipid modifying drug hmg coa reductase inhibitors Drugs 0.000 title abstract 2
150000001875 compounds Chemical class 0.000 claims abstract description 51
-1 triphenylsilyl Chemical group 0.000 claims abstract description 14
125000000217 alkyl group Chemical group 0.000 claims abstract description 13
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims abstract description 8
125000001309 chloro group Chemical group Cl* 0.000 claims abstract description 7
125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims abstract description 6
125000006239 protecting group Chemical group 0.000 claims abstract description 6
125000004183 alkoxy alkyl group Chemical group 0.000 claims abstract description 5
125000005081 alkoxyalkoxyalkyl group Chemical group 0.000 claims abstract description 5
125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims abstract description 5
125000001246 bromo group Chemical group Br* 0.000 claims abstract 3
JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 claims description 6
238000000034 method Methods 0.000 claims description 6
XJUZRXYOEPSWMB-UHFFFAOYSA-N Chloromethyl methyl ether Chemical compound COCCl XJUZRXYOEPSWMB-UHFFFAOYSA-N 0.000 claims description 2
229940061627 chloromethyl methyl ether Drugs 0.000 claims description 2
238000004519 manufacturing process Methods 0.000 claims description 2
239000000126 substance Substances 0.000 claims 2
KXASUGRAQCHJLA-YADHBBJMSA-N ethyl (3r,5s)-6-bromo-5-[tert-butyl(diphenyl)silyl]oxy-3-(methoxymethoxy)hexanoate Chemical compound C=1C=CC=CC=1[Si](C(C)(C)C)(O[C@H](CBr)C[C@H](CC(=O)OCC)OCOC)C1=CC=CC=C1 KXASUGRAQCHJLA-YADHBBJMSA-N 0.000 claims 1
NQUSXUDKEXCHEU-UXHICEINSA-N ethyl (3r,5s)-6-bromo-5-[tert-butyl(diphenyl)silyl]oxy-3-hydroxyhexanoate Chemical compound C=1C=CC=CC=1[Si](C(C)(C)C)(O[C@H](CBr)C[C@@H](O)CC(=O)OCC)C1=CC=CC=C1 NQUSXUDKEXCHEU-UXHICEINSA-N 0.000 claims 1
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 44
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 27
XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 24
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 18
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 18
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 17
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 16
101150041968 CDC13 gene Proteins 0.000 description 14
HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 14
239000011541 reaction mixture Substances 0.000 description 14
239000000243 solution Substances 0.000 description 13
229910052786 argon Inorganic materials 0.000 description 12
OAYLNYINCPYISS-UHFFFAOYSA-N ethyl acetate;hexane Chemical compound CCCCCC.CCOC(C)=O OAYLNYINCPYISS-UHFFFAOYSA-N 0.000 description 12
229910001868 water Inorganic materials 0.000 description 12
239000012267 brine Substances 0.000 description 11
239000000463 material Substances 0.000 description 11
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 11
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 11
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 10
239000000203 mixture Substances 0.000 description 9
229910052943 magnesium sulfate Inorganic materials 0.000 description 8
229910000030 sodium bicarbonate Inorganic materials 0.000 description 8
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 8
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 7
239000012044 organic layer Substances 0.000 description 7
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 6
QMMFVYPAHWMCMS-UHFFFAOYSA-N Dimethyl sulfide Chemical compound CSC QMMFVYPAHWMCMS-UHFFFAOYSA-N 0.000 description 6
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 6
238000001035 drying Methods 0.000 description 6
125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 6
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 6
239000002253 acid Substances 0.000 description 5
238000004587 chromatography analysis Methods 0.000 description 5
239000001257 hydrogen Substances 0.000 description 5
229910052739 hydrogen Inorganic materials 0.000 description 5
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 5
239000000047 product Substances 0.000 description 5
238000000746 purification Methods 0.000 description 5
229920006395 saturated elastomer Polymers 0.000 description 5
239000002904 solvent Substances 0.000 description 5
ABQPEYRVNHDPIO-UHFFFAOYSA-N bromo(dimethyl)borane Chemical compound CB(C)Br ABQPEYRVNHDPIO-UHFFFAOYSA-N 0.000 description 4
239000012043 crude product Substances 0.000 description 4
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 3
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 3
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
238000006243 chemical reaction Methods 0.000 description 3
229910052681 coesite Inorganic materials 0.000 description 3
238000001816 cooling Methods 0.000 description 3
229910052906 cristobalite Inorganic materials 0.000 description 3
229960004132 diethyl ether Drugs 0.000 description 3
239000000499 gel Substances 0.000 description 3
150000004820 halides Chemical class 0.000 description 3
FUZZWVXGSFPDMH-UHFFFAOYSA-N hexanoic acid Chemical compound CCCCCC(O)=O FUZZWVXGSFPDMH-UHFFFAOYSA-N 0.000 description 3
239000012442 inert solvent Substances 0.000 description 3
150000002500 ions Chemical class 0.000 description 3
150000002596 lactones Chemical group 0.000 description 3
AJLFOPYRIVGYMJ-INTXDZFKSA-N mevastatin Chemical compound C([C@H]1[C@@H](C)C=CC2=CCC[C@@H]([C@H]12)OC(=O)[C@@H](C)CC)C[C@@H]1C[C@@H](O)CC(=O)O1 AJLFOPYRIVGYMJ-INTXDZFKSA-N 0.000 description 3
239000000377 silicon dioxide Substances 0.000 description 3
235000012239 silicon dioxide Nutrition 0.000 description 3
238000003756 stirring Methods 0.000 description 3
229910052682 stishovite Inorganic materials 0.000 description 3
229910052905 tridymite Inorganic materials 0.000 description 3
238000010792 warming Methods 0.000 description 3
JYVXNLLUYHCIIH-UHFFFAOYSA-N (+/-)-mevalonolactone Natural products CC1(O)CCOC(=O)C1 JYVXNLLUYHCIIH-UHFFFAOYSA-N 0.000 description 2
BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 2
RGLQSFFFIREZFV-UHFFFAOYSA-N 1-(bromomethyl)-2,4-dichlorobenzene Chemical compound ClC1=CC=C(CBr)C(Cl)=C1 RGLQSFFFIREZFV-UHFFFAOYSA-N 0.000 description 2
MEKOFIRRDATTAG-UHFFFAOYSA-N 2,2,5,8-tetramethyl-3,4-dihydrochromen-6-ol Chemical compound C1CC(C)(C)OC2=C1C(C)=C(O)C=C2C MEKOFIRRDATTAG-UHFFFAOYSA-N 0.000 description 2
DZAIOXUZHHTJKN-UHFFFAOYSA-N 2-Desoxy-D-glycero-tetronsaeure Natural products OCC(O)CC(O)=O DZAIOXUZHHTJKN-UHFFFAOYSA-N 0.000 description 2
VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 2
HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 2
NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 2
VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 2
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
VGMFHMLQOYWYHN-UHFFFAOYSA-N Compactin Natural products OCC1OC(OC2C(O)C(O)C(CO)OC2Oc3cc(O)c4C(=O)C(=COc4c3)c5ccc(O)c(O)c5)C(O)C(O)C1O VGMFHMLQOYWYHN-UHFFFAOYSA-N 0.000 description 2
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 2
PCZOHLXUXFIOCF-UHFFFAOYSA-N Monacolin X Natural products C12C(OC(=O)C(C)CC)CC(C)C=C2C=CC(C)C1CCC1CC(O)CC(=O)O1 PCZOHLXUXFIOCF-UHFFFAOYSA-N 0.000 description 2
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
JYVXNLLUYHCIIH-ZCFIWIBFSA-N R-mevalonolactone, (-)- Chemical group C[C@@]1(O)CCOC(=O)C1 JYVXNLLUYHCIIH-ZCFIWIBFSA-N 0.000 description 2
AJLFOPYRIVGYMJ-UHFFFAOYSA-N SJ000287055 Natural products C12C(OC(=O)C(C)CC)CCC=C2C=CC(C)C1CCC1CC(O)CC(=O)O1 AJLFOPYRIVGYMJ-UHFFFAOYSA-N 0.000 description 2
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
KCGZWRHOWBAXMW-UHFFFAOYSA-M [Br-].[Mg+]CC1=CC=C(Cl)C=C1Cl Chemical compound [Br-].[Mg+]CC1=CC=C(Cl)C=C1Cl KCGZWRHOWBAXMW-UHFFFAOYSA-M 0.000 description 2
235000019270 ammonium chloride Nutrition 0.000 description 2
238000004458 analytical method Methods 0.000 description 2
125000004429 atom Chemical group 0.000 description 2
125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 description 2
UWTDFICHZKXYAC-UHFFFAOYSA-N boron;oxolane Chemical compound [B].C1CCOC1 UWTDFICHZKXYAC-UHFFFAOYSA-N 0.000 description 2
230000003197 catalytic effect Effects 0.000 description 2
150000004696 coordination complex Chemical class 0.000 description 2
238000010828 elution Methods 0.000 description 2
238000000855 fermentation Methods 0.000 description 2
230000004151 fermentation Effects 0.000 description 2
238000003818 flash chromatography Methods 0.000 description 2
125000005843 halogen group Chemical group 0.000 description 2
150000002431 hydrogen Chemical class 0.000 description 2
238000007273 lactonization reaction Methods 0.000 description 2
PCZOHLXUXFIOCF-BXMDZJJMSA-N lovastatin Chemical compound C([C@H]1[C@@H](C)C=CC2=C[C@H](C)C[C@@H]([C@H]12)OC(=O)[C@@H](C)CC)C[C@@H]1C[C@@H](O)CC(=O)O1 PCZOHLXUXFIOCF-BXMDZJJMSA-N 0.000 description 2
QLJODMDSTUBWDW-UHFFFAOYSA-N lovastatin hydroxy acid Natural products C1=CC(C)C(CCC(O)CC(O)CC(O)=O)C2C(OC(=O)C(C)CC)CC(C)C=C21 QLJODMDSTUBWDW-UHFFFAOYSA-N 0.000 description 2
229940057061 mevalonolactone Drugs 0.000 description 2
BOZILQFLQYBIIY-UHFFFAOYSA-N mevastatin hydroxy acid Natural products C1=CC(C)C(CCC(O)CC(O)CC(O)=O)C2C(OC(=O)C(C)CC)CCC=C21 BOZILQFLQYBIIY-UHFFFAOYSA-N 0.000 description 2
230000003287 optical effect Effects 0.000 description 2
CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 2
239000000376 reactant Substances 0.000 description 2
229910000342 sodium bisulfate Inorganic materials 0.000 description 2
239000007858 starting material Substances 0.000 description 2
FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 2
JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 2
OZJMQIQYJAAFPE-CHWSQXEVSA-N (3R,5R)-7-(2,4-dichlorophenyl)-5-hydroxy-3-(methoxymethoxy)heptanoic acid Chemical compound COCO[C@@H](CC(O)=O)C[C@H](O)CCC1=CC=C(Cl)C=C1Cl OZJMQIQYJAAFPE-CHWSQXEVSA-N 0.000 description 1
CABVTRNMFUVUDM-VRHQGPGLSA-N (3S)-3-hydroxy-3-methylglutaryl-CoA Chemical compound O[C@@H]1[C@H](OP(O)(O)=O)[C@@H](COP(O)(=O)OP(O)(=O)OCC(C)(C)[C@@H](O)C(=O)NCCC(=O)NCCSC(=O)C[C@@](O)(CC(O)=O)C)O[C@H]1N1C2=NC=NC(N)=C2N=C1 CABVTRNMFUVUDM-VRHQGPGLSA-N 0.000 description 1
SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 1
YJTKZCDBKVTVBY-UHFFFAOYSA-N 1,3-Diphenylbenzene Chemical group C1=CC=CC=C1C1=CC=CC(C=2C=CC=CC=2)=C1 YJTKZCDBKVTVBY-UHFFFAOYSA-N 0.000 description 1
PDGCLGBJPAEBTK-UHFFFAOYSA-N 2,3-dihydroxyhex-2-enoic acid Chemical compound CCCC(O)=C(O)C(O)=O PDGCLGBJPAEBTK-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
ZOXJGFHDIHLPTG-UHFFFAOYSA-N Boron Chemical compound [B] ZOXJGFHDIHLPTG-UHFFFAOYSA-N 0.000 description 1
CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 1
QWOJMRHUQHTCJG-UHFFFAOYSA-N CC([CH2-])=O Chemical compound CC([CH2-])=O QWOJMRHUQHTCJG-UHFFFAOYSA-N 0.000 description 1
XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 1
XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 1
241001547070 Eriodes Species 0.000 description 1
KRHYYFGTRYWZRS-UHFFFAOYSA-M Fluoride anion Chemical compound [F-] KRHYYFGTRYWZRS-UHFFFAOYSA-M 0.000 description 1
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 1
102000004286 Hydroxymethylglutaryl CoA Reductases Human genes 0.000 description 1
108090000895 Hydroxymethylglutaryl CoA Reductases Proteins 0.000 description 1
FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
229910017974 NH40H Inorganic materials 0.000 description 1
238000006859 Swern oxidation reaction Methods 0.000 description 1
XSTXAVWGXDQKEL-UHFFFAOYSA-N Trichloroethylene Chemical compound ClC=C(Cl)Cl XSTXAVWGXDQKEL-UHFFFAOYSA-N 0.000 description 1
230000002378 acidificating effect Effects 0.000 description 1
150000007513 acids Chemical class 0.000 description 1
229910052783 alkali metal Inorganic materials 0.000 description 1
150000001340 alkali metals Chemical class 0.000 description 1
150000004703 alkoxides Chemical class 0.000 description 1
230000000326 anti-hypercholesterolaemic effect Effects 0.000 description 1
125000003118 aryl group Chemical group 0.000 description 1
125000004391 aryl sulfonyl group Chemical group 0.000 description 1
125000002619 bicyclic group Chemical group 0.000 description 1
239000004305 biphenyl Substances 0.000 description 1
229910052796 boron Inorganic materials 0.000 description 1
239000001273 butane Substances 0.000 description 1
150000008280 chlorinated hydrocarbons Chemical class 0.000 description 1
238000013375 chromatographic separation Methods 0.000 description 1
239000013078 crystal Substances 0.000 description 1
150000002009 diols Chemical class 0.000 description 1
238000004821 distillation Methods 0.000 description 1
230000000694 effects Effects 0.000 description 1
150000002118 epoxides Chemical class 0.000 description 1
238000011067 equilibration Methods 0.000 description 1
150000002170 ethers Chemical class 0.000 description 1
229940052303 ethers for general anesthesia Drugs 0.000 description 1
HHFAWKCIHAUFRX-UHFFFAOYSA-N ethoxide Chemical compound CC[O-] HHFAWKCIHAUFRX-UHFFFAOYSA-N 0.000 description 1
239000000284 extract Substances 0.000 description 1
125000001153 fluoro group Chemical group F* 0.000 description 1
229930195733 hydrocarbon Natural products 0.000 description 1
150000002430 hydrocarbons Chemical class 0.000 description 1
239000003112 inhibitor Substances 0.000 description 1
230000002401 inhibitory effect Effects 0.000 description 1
230000000977 initiatory effect Effects 0.000 description 1
229910052740 iodine Inorganic materials 0.000 description 1
239000011630 iodine Substances 0.000 description 1
230000000670 limiting effect Effects 0.000 description 1
229910052744 lithium Inorganic materials 0.000 description 1
235000019341 magnesium sulphate Nutrition 0.000 description 1
238000002844 melting Methods 0.000 description 1
230000008018 melting Effects 0.000 description 1
229910052751 metal Inorganic materials 0.000 description 1
239000002184 metal Substances 0.000 description 1
238000006140 methanolysis reaction Methods 0.000 description 1
NSPJNIDYTSSIIY-UHFFFAOYSA-N methoxy(methoxymethoxy)methane Chemical class COCOCOC NSPJNIDYTSSIIY-UHFFFAOYSA-N 0.000 description 1
WZZMHOBVLAEJOD-UHFFFAOYSA-N methylsulfanylmethane;hydrobromide Chemical compound [Br-].C[SH+]C WZZMHOBVLAEJOD-UHFFFAOYSA-N 0.000 description 1
230000005012 migration Effects 0.000 description 1
238000013508 migration Methods 0.000 description 1
150000007522 mineralic acids Chemical class 0.000 description 1
229930014626 natural product Natural products 0.000 description 1
125000001181 organosilyl group Chemical group [SiH3]* 0.000 description 1
230000036961 partial effect Effects 0.000 description 1
230000037361 pathway Effects 0.000 description 1
230000003389 potentiating effect Effects 0.000 description 1
239000002244 precipitate Substances 0.000 description 1
230000001681 protective effect Effects 0.000 description 1
239000012264 purified product Substances 0.000 description 1
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
230000002829 reductive effect Effects 0.000 description 1
238000010992 reflux Methods 0.000 description 1
229910002027 silica gel Inorganic materials 0.000 description 1
239000000741 silica gel Substances 0.000 description 1
229910052814 silicon oxide Inorganic materials 0.000 description 1
239000002002 slurry Substances 0.000 description 1
229910052708 sodium Inorganic materials 0.000 description 1
235000017557 sodium bicarbonate Nutrition 0.000 description 1
239000011780 sodium chloride Substances 0.000 description 1
QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 1
241000894007 species Species 0.000 description 1
239000012258 stirred mixture Substances 0.000 description 1
125000005207 tetraalkylammonium group Chemical group 0.000 description 1
IIHPVYJPDKJYOU-UHFFFAOYSA-N triphenylcarbethoxymethylenephosphorane Chemical compound C=1C=CC=CC=1P(C=1C=CC=CC=1)(=CC(=O)OCC)C1=CC=CC=C1 IIHPVYJPDKJYOU-UHFFFAOYSA-N 0.000 description 1
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 1
238000005406 washing Methods 0.000 description 1
238000010626 work up procedure Methods 0.000 description 1

Classifications

- 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

Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)

CA000546907A 1984-11-19 1987-09-15 Intermediaires utilises dans la preparation d'inhibiteurs de la reductase hmg-coa Expired - Lifetime CA1273352A (fr)

Priority Applications (1)

Application Number	Priority Date	Filing Date	Title
CA000546907A CA1273352A (fr)	1984-11-19	1987-09-15	Intermediaires utilises dans la preparation d'inhibiteurs de la reductase hmg-coa

Applications Claiming Priority (4)

Application Number	Priority Date	Filing Date	Title
US673,231		1984-11-19
US06/673,231 US4611068A (en)	1984-11-19	1984-11-19	Process for the preparation of HMG-CoA reductase inhibitors and intermediate compounds employed therein
CA000495158A CA1245226A (fr)	1984-11-19	1985-11-13	Procede de preparation d'inhibiteurs de la hmg-coa reductase et composes intermediaires
CA000546907A CA1273352A (fr)	1984-11-19	1987-09-15	Intermediaires utilises dans la preparation d'inhibiteurs de la reductase hmg-coa

Related Parent Applications (1)

Application Number	Title	Priority Date	Filing Date
CA000495158A Division CA1245226A (fr)	1984-11-19	1985-11-13	Procede de preparation d'inhibiteurs de la hmg-coa reductase et composes intermediaires

Publications (1)

Publication Number	Publication Date
CA1273352A true CA1273352A (fr)	1990-08-28

Family

ID=25670835

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
CA000546907A Expired - Lifetime CA1273352A (fr)	1984-11-19	1987-09-15	Intermediaires utilises dans la preparation d'inhibiteurs de la reductase hmg-coa

Country Status (1)

Country	Link
CA (1)	CA1273352A (fr)

1987
- 1987-09-15 CA CA000546907A patent/CA1273352A/fr not_active Expired - Lifetime

Legal Events

Date	Code	Title	Description
1994-02-28	MKLA	Lapsed

Publication	Publication Date	Title
US5334740A (en)	1994-08-02	Cyclohexanetriol derivatives
Tietze et al.	1996	Stereodivergent Hetero‐Diels‐Alder Reactions of Chiral 1‐Oxa‐1, 3‐butadienes through a Conformational Switch Induced by Lewis Acids
IL98190A (en)	1995-12-31	Process for the stereoselective preparation of phenylisoserine derivatives
US4611068A (en)	1986-09-09	Process for the preparation of HMG-CoA reductase inhibitors and intermediate compounds employed therein
CA1340430C (fr)	1999-03-09	Preparation de tetrazoles antihypercholesterolemiques et leurs intermediaires
US7345181B2 (en)	2008-03-18	Process for preparing prostaglandin derivatives and starting materials for the same
US4855481A (en)	1989-08-08	Process for the preparation of HMG-CoA reductase inhibitors and intermediate compounds employed therein
JPH05178849A (ja)	1993-07-20	光学活性な含フッ素化合物
CA1273352A (fr)	1990-08-28	Intermediaires utilises dans la preparation d'inhibiteurs de la reductase hmg-coa
Ito et al.	2006	Enantioselective total synthesis of both diastereomers of preclavulone-A methyl ester
CA1307264C (fr)	1992-09-08	Intermediaires et procedes pour la fabrication d'inhibiteurs 6-carboxy de la hmg-coa reductase
JPH054943A (ja)	1993-01-14	光学活性β，δ−ジケト酸エステル及びその還元体
CA1307534C (fr)	1992-09-15	Composes intermediaires utiles pour la preparation d'inhibiteurs de la hmg-coa reductase
US4582914A (en)	1986-04-15	Process for the preparation of HMG-CoA reductase inhibitors
KR100322630B1 (ko)	2002-08-21	심바스타틴및 이의 중간체 화합물을 제조하는 방법
US4701536A (en)	1987-10-20	Novel 10-membered ring compound and process for preparing the same
JPH0245614B2 (fr)	1990-10-11
JPWO2005058859A1 (ja)	2007-12-13	３−（４−テトラヒドロピラニル）−３−オキソプロパン酸アルキル化合物及び４−アシルテトラヒドロピランの製法
KR20090044817A (ko)	2009-05-07	(6ｒ)-3-헥실-4-히드록시-6-운데실-5,6-다이히드로피란-2-온의 제조방법 및 이에 사용되는 중간체
US4985571A (en)	1991-01-15	6-membered lactones useful as intermediates for antilipemic mevalonic acid lactones
JPS6293285A (ja)	1987-04-28	ピラン誘導体及びその製法
JP3097678B2 (ja)	2000-10-10	アファノルフィン中間体
US5149835A (en)	1992-09-22	Substituted mevalonolactones, and methods for stereoselective preparation thereof and desmethyl homologues thereof
JP2843430B2 (ja)	1999-01-06	環状セスキテルペン及びその製造法
JPH0224274B2 (fr)	1990-05-29