CS251657B1 - Preparation method of the 11a-chlorine-5-hydroxytetracyclone-6,12-hemiketale - Google Patents
Preparation method of the 11a-chlorine-5-hydroxytetracyclone-6,12-hemiketale Download PDFInfo
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- CS251657B1 CS251657B1 CS833524A CS352483A CS251657B1 CS 251657 B1 CS251657 B1 CS 251657B1 CS 833524 A CS833524 A CS 833524A CS 352483 A CS352483 A CS 352483A CS 251657 B1 CS251657 B1 CS 251657B1
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- preparation
- mol
- hydroxytetracyclone
- hemiketale
- chlorine
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- 238000002360 preparation method Methods 0.000 title claims 2
- 238000000034 method Methods 0.000 claims 4
- 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 claims 1
- 239000004100 Oxytetracycline Substances 0.000 claims 1
- 150000001447 alkali salts Chemical class 0.000 claims 1
- 238000006243 chemical reaction Methods 0.000 claims 1
- 239000007795 chemical reaction product Substances 0.000 claims 1
- 239000012320 chlorinating reagent Substances 0.000 claims 1
- 238000005660 chlorination reaction Methods 0.000 claims 1
- 159000000011 group IA salts Chemical class 0.000 claims 1
- 238000002955 isolation Methods 0.000 claims 1
- IWVCMVBTMGNXQD-PXOLEDIWSA-N oxytetracycline Chemical compound C1=CC=C2[C@](O)(C)[C@H]3[C@H](O)[C@H]4[C@H](N(C)C)C(O)=C(C(N)=O)C(=O)[C@@]4(O)C(O)=C3C(=O)C2=C1O IWVCMVBTMGNXQD-PXOLEDIWSA-N 0.000 claims 1
- 229960000625 oxytetracycline Drugs 0.000 claims 1
- 235000019366 oxytetracycline Nutrition 0.000 claims 1
- 238000004062 sedimentation Methods 0.000 claims 1
- 229910052708 sodium Inorganic materials 0.000 claims 1
- 239000011734 sodium Substances 0.000 claims 1
- 239000002904 solvent Substances 0.000 claims 1
- IWVCMVBTMGNXQD-UHFFFAOYSA-N terramycin dehydrate Natural products C1=CC=C2C(O)(C)C3C(O)C4C(N(C)C)C(O)=C(C(N)=O)C(=O)C4(O)C(O)=C3C(=O)C2=C1O IWVCMVBTMGNXQD-UHFFFAOYSA-N 0.000 claims 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 229920002943 EPDM rubber Polymers 0.000 description 1
- 101100172132 Mus musculus Eif3a gene Proteins 0.000 description 1
- 241001089215 Notomys Species 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
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- Crystals, And After-Treatments Of Crystals (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Description
1
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OfíjiaCTb ΠρΗΜβΗβΗΗΠ Η3θβρβΤβΗΜΛ Η3θ6ρβτβΗΗβ KacaeTCH cnocoOa nójiyueHHH 11 a-xjiop-5-rHflpoKCHTeTpanHKnHH-6,12-reMM-KfiTajiH nyTeM xjiopHpoBaHHH S-rHflpoKCHTeTpanHKBHHa. IIonyHaeMbiřt τβκημ o6pa3OM 1 ía-Knop-5-rH/ípoKCHTeTpanHKjiHH-6,12-reMHKeTajib moxho H3BecTHbiM oSpaaoM npeBpaTHTbB 6-MeTHneH~6-,HHMeTHn~6-ne3OKCH-5“rHflpOKCH-TeTpaUHKJlHH, HBJlHWmHňCH UeHHblM aHTH— .6HOTHKOM,
XapaKTepHCTHKa Η3βθοτημχ TexHHnecKHX pemeHU# fljiH nojiyqeHHH I la-xjiop-5-rnflpoKCHTeTpauHKJiHH-6,12- reMHKgTanH npennoxeHo yxe He-cxojibKO cnocofioB (U.S.P. 2984 686, DE-OS 2 164 840, DD-AP 113 527). B οοοτΒβτ-ctbhh co bc6mh npejvtoxeHHbíMH cnocofíaMH 5-rHflpoKCHTeTpaiíHKjiHH xjiopHpyioT b peaK-μΗΟΗΗΟ-ίΉΗβρΤΗΟΜ, CMePlHBaFHHeMCH C BOflOň paCTBQpHT&Jie, ΠρΗΗβΜ HKO6bI MOryT npHMe-HHŤbCH cňeflywDpie xjiopHpjnoncHe BeinecTBa: xnop, aMHflw N-xjiop-HH3KoajiKanoBoň khcjio-Tbl, HMHflbl XJlOpflHKapBOHOBOň KHCJIOTM, N-HH3KOaJlKaHOHJiaHHJIHflbI, XJIÓpflHMeTHnrHflaHTO-jíh, nepxjiopnHpHflHHOBHÍi rHflpoxnopHfl h HH3inne · ajiKHJirHnoxjiopuTbi. CornacHo cnocoCyIj.S.P. 2 984 686 - xjiopHposaHHe 5-rHflpoKCHTeŤpauHKJiHHa kaK ocHOBaHHH πρπ TeMne-paTypax 0 - 50°C - nojiyxeHM Jiranb cpaBHHTejibHO HH3Kne Bbixoflbí (okojio 40% TěopHH),τβκ κβκ nacTb nponyKTa xjiopHpoBaHHH nonynaeTCH b MaJiocTa6HJibHoii κετοφορΜβ. BcooTBeTCTBHH Co cnocofíoM DE-OS 2 164 840 o6pa6oTKoň peaKiiHOHHoň cMecu τρηβτηπ-aMMHOBbíM 6y$epoM no pH 3 - 5, npeflnoHTHTeJibHO 4 - 4,5, b peeyjibTaTe xjiopHposa-hhh b npeflejiax -15 po -4®C nonynaioT JiyBunoi Bbixop sa cneT cnoHTaHHoň KpHCTanjiH-3aiJHH CTaOnjlbHOií SHOJIbHOH φθρΜΜ* B OTJIHHHe OT 3Τ0Γ0, cnoco6 COmaCHO DD-AP113 527 npeflycMaTpHBaeT xjiopupoBaHHe tipneme 6onee hh3khx TeMnepaTypax (-40°C) H o6pa6oTKy peaKiíHOHHOň cmsch 6ojiee cwibHMM τρη3τκπ3μβΗοβημ 6y<l>epoM ro pH = “ 6,5 - 7,7, b nacTHocTH 7,3 - 7,5, H ocaxpeHHe npoflyKTa peaKUHH H3 peaKiiHOHHott CMeCH B Ka^eCTBe COJTH SHOJTbHOÍÍ <J)OpMbI C MHHepajIbHOň KHCJTOTOK C BbIXOflOM οκοπο78% ΤβΟρΗΗ. JBih scex npexHHX cnocofios, Hapn^y c πρΗΜβΗβΗΗβΜ cMeniHBawiuHXCH c bojích pacTBopH-
TeJiéft, ofinu®* HBJweTCH npennoHHTaeMoe b ππτβΗτΗΜΧ <t>opMynax h onHCbmaeMoe hckjtw-ΊΗΤβπΒΗο B npHMepax ocynecTBJíeHHH Htcn0Jib3OBaHne N—xjiopcyKtjHHHMHfla b Ka^ecTBe 251657 2 xnopupyrauero BewecTBa, xoth sto BeiqecTBo naneKo ne HBjínercH Han6ojiee peHTa6enb-HblM H3 Bcex ΠρηβΜΠβΜΗΧ CpeflCTB ΧΠΟρΗρΟΒΗΗΗΗ. flpyrne cpeflCTBa xnopupoBaHHH^ Ha3HBaeMMe b HBBecTHblx npennaraeMbix cnoco6ax, XOTH H MOryT RbtTb HCnOJIbaOBaHH &ΠΗ XJIOpHpOBaHBH, ΒΜβΟΤΟ N-XJTOpCyKBHHHMHfla, HOBáwT npHHHHnHajibHo Ronee ηη3κηθ βηχοημ, neM Nr-xnopcyKUHHHMHn. fljia cneijHanbHMxBejieň xnopupoBaHHH ncnonb3OBanHCb Taxxe. ywe h aMHflbí H Ν-χπορ- η N,N-nHXJiopapHji-cyjibfJiOHOBOH khcjiotm (cm. Houben, Weyl, Methoden der organischen Chemie, GeorgThieme Verlag Stuttgart, 4, Auflage Bd, V/3, S. 808 ff. u» Bd, IX S. 645). 3th coeflHHeHHH, KOTopbie, oueBHnHo, enje He HcnojibaoBajiHCb po chx nop íwh xjioph-poBaHHB 5~rnBpoKCH-TeTpanHKBHHa, mowho HcnojibaůBaTb Taxxe, κβκ h N-XJiopeyKUHH-HMHfl, ho ohh ne ofijianaioT ηηκλκημη npeHMymecTBaMH no cpaBHeHHto c nocJteflHHM.
KpoMe toto, ofia cnocofia corjiacHo DE-OS 2 164 8,40 h DD-AP 113 527, ocymeCTBnae-Mbie c yBOBBtíTBopHTenbHWM bhxoaom, TpefiytoT τοηηογο cofijnoneHHH y3KHX npeflenoB3HaneHHH pH, oneBH/xHO, aaBHCHMNx ot nannoro cnocofia. OflHaxo, xaK noKaawBaeTojibiT, H3MepeHHe 3HaqenHH pH cBHaaHo co 3HauHTenbHbiMH TpyflHOCTHMH b npoH3BOflCT-BeHHoň npaxTHKe npH pacTBopax, He coflepxawux Bony hbh coflepJKamHX He3HaHHTejtbHoeKonnuecTBo BOflH, τβΜ fionee npH TeMnepaTypax tuwe -5°C.
Uejlb Η3θ6ρβΤβΗΗΗ
Uejibw npeftnaraeMoro Η3θ6ρβτβΗΗΗ ΗΒΠΗβτοπ cnocofi nonyneHMa I la-xnop-S-rHgpoKCH-TeTpanHKBHH-6,12-reMHKeTaJiH TexHojiornnecKH npocTttM cnocofioM h c Hcnojib3OpaHHeMfiojiee fleineBoro cpegcTBa xnopupoBaHHH no cpaBHeHHto c N-xnopcyKUHHHMHBOM. Πρρ#γκτ,npH 3TOM, flojmeH fíbiTb nojiyHtíH, no xpaňHeň Mepe, c T8khm jte BbtxonoM, xatc h nonyniUHM H3 H3BeCTHHX CnOCOfíOB, B 3HOJIbHOřt φΟρΜβ.
HanoweHHe cymnocTH Η3θβρβτβΗΗΗ 3aflaua 3aKJnonajiacb b tom, hto6h HaňTH ηοβοθ, fionee nemeBoe cpencTBO xnopupoBa-hhh, κοτοροβ no3BonH.no 6bi fie3 3aTpyflHeHHň b ycTanoBKe npenenos pH c bmcokhmBbixoflOM npoBecTH xnopHpoBaHHe 5-rHflpoKCHTeTpanHKjiHHa b xenaeMbiň 11 a-xjiop-S-THflp-,OKCH-TeTpanHKJiHH-6,12-reMHKeTaJib.
PeuiHTb 3aflany η6οβηβ;βηηο y/vuioch τβΜ, hto fiuno naň^eHo, hto menoHHbte cojih N-MOHOXJlOpapHJICyjIb<í)OHaMHBOB HBJIHWTCH OTJIHHHblMH CpeflCTBaMH ΧΠΟρΗρΟΒΗΗΗΗ 5~ΓΗβρθΚ-ch-TeTpanHKJiHHa b nonoxeHHH 11a c ofipasoBaHHeM 6,12-reMHKeTajia b οηοπβηοη φόρΜβ,ΧΟΤΗ 3TH COeBHHeHHH HapHfly G HX KOMMepBeCKHM ΠΡΗΜβΗβΗΗβΜ B KaBeCTBe fle3HH<í)HIj(H“pytomHX cpeflCTB flo chx nop HcnoJib3OBajiHCb b xanecTBe OKHCHHTeJieň, ho ne xax cpefl-cTBa xnopHpoBaHHH (Houben-Weyl, Methoden der organischen Chemie Bd, IX S. 644),yflHBJíHJio η το, hto ofipa3OBanca xejiaeMbiň προπγκτ xnopHpoBaHHH BbtcoKorO KanecTBaH C OTJIHUHHM ΒΗΧΟ^ΟΜ 6β3 yCTaHOBKH OflHOrO H3 flO CHX ΠΟρ ΠρΗ3Η3ΗΗΕ1Χ ΟΠΤΗΜβΠΒΗΗΜΗ ·npeflejioB 3HaneHHň pH (4-4,5 ηπη 7,3-7,5) po hjjh bo BpeMH peaKiwH.
HanpuMep, npn Hcnojib3OBaHHH tnenouHbix coneň N-xnopcynbtitoHaMHjia b ycnoBHHX yxa-áaHHbix b DD-AP 1 13 527 nonynawT 1 la-xjiop-6,12-reMHKeTanb c bmxobom πηπιβ οκοπο60%, h c BbicoKoň floneň HeKenaTenbHoň κβτοφορΜΜ, B yenOBHHX xe npH3HaHHNX Η3θ6ρβΤβΗΗβΜ OnTHManhHblMH BbIXOfl Ha 5% Bbnne, HeM cornac-ho DD-AP 113 527.
HeoKHflaHHHM fiwno rnanKoe προτβκβΗΗβ peaKUHH h noTOMy, hto cšmh no ce6e cnnbHOnonnpHbie conn TpygHo pacTBópHMH b opraHHHecKHx pacTBOpax, conepjKamHX πηππ» He-3HanHTenbHoe KonimecTBO βολμ h TeMnepaTypax peaxuHH* 0co6o BMroflHHM npeflCTaBHTeneM ηηββηηηογο Knacca coeflHHeHwS ηβπηθτοη N-xnop-n-Tonyoncynb(íioHaMH,nHHň HaTpHft (τορτοΒοβ-HaasaHMe xnopaMHH T). PeaKium c bhm npo-TexaeT b oneHb μηγκηχ ycnoBHHX aa oxéHb κοροτκοβ βρθμη πηηιβ cna6o3K3OTepMH5tec“ 251657 3 κη η 6jih3Ko κ KojiHxecTBeHHoň c ποπγπβΗΗβΜ pacTBopa 11 a-xnop-5-rHnpoKCH-TeTpa-UHKJihh-6 ,12-reMHKeTajiH, IIpeHMyiuecTBO ncnonb3OBaHHH aMHflHbixt coneň Ν-χπορ-3ριπιογπ&φθΗθΒθή khcjiotw b3Toň peaKiuw npoHBHnocb h b tom, hto pacTBop ηπη cycneH3Hio 5-ΓΗηροκςΗ-τβτρβιχΗΚ-JiHHa cjieflyer oxnajtnaTb tojibko onHH pas, HanpHMep, b 6e3BonHOM aneTOHe no τβΜ-nepaTypw -1O...-4O°C, a πρκ npHfiaBneHHH cpencTBa xnopnpOBaHHH He cnenyeT najibmeqxjiaxnaTb. Πρκ 3tom TeMnepaTypa BoapacT&na no -15...+5°C. HHTepecHbíMH 6μπη pe-3yjibTarbi H3MepeHHH pH b peaKipťbHHoíi cMecH. B cnynae ncnojib3OBanMR Heo6xonnMoroΑΠΗ nOCTHXeHHH ΧΟρΟΙΠβΓΟ BMXOna KOJBfyeCTBa N-MOHOXJIOp-n-TOJTyOJlCyjlb$OHaMHnHOrOΗΗτρκΗ πορπηκβ 1,1 no 1,3 moji Ha moji S-rnnpoKCH-TeTpaUHKJiHHa nojiynHJiH 3HaqeHnepH 5,1-6,3. IIpH npennoHTHTejibKOM κοπκηβοτΒβ cpencTBa xnopHpoBaHHH b 1,2 moji no-JiyuHjiH 3HaneHHe pH, paeHoe 5,8, T.e. 3HaHeHne, κοτοροβ He naeT o»nnaeMbix pe3yjib-~T3TOB HpH paCoTe no H3B€CTHMM CnOCO6aM. HeOJKHnaHHO CbUlO, Hro 6bUI nOCTHTHyT xopo“iunň Bbixon h KanecTBO nponyKTa, HecMOTpa Ha to, hto ycTaHaBJíHBaeMoe 3HaneHHepH (5,1 ηθ 6,3) b cnocoCe, cornacno Η3θβρβτβΗΐοο, ne neacHT b oSnacTH pH HaftnenHoftxax oitTHMaJibHoň bo Bcex npenraecTBywmHX cnocoGax (pH = 3 no 5 DE-OS 2 164 840 hpH * 6,5 no 7,7 corjiacHo DD-AP 113 527).
PeiuaraÍHHM npeHMymecTBOM no cpaaHeHHio c ypoBHeM τθχηηκη ηβπηθτοβ raKace το, htooTnanaeT HeoSxonHMocTb b H3MepeHHH 3HaueHHH pH.
UsMepenne pH πρκ TeMnepaTypax Hiáte -10°C no chx nop He ηβπηθτοη HeynoBJíeTBOpH-TejibHo peraeHHoň npoBjíeMoň H3Mepemut. H3JiHpoBanHe nponyKTa mojkho oeymecTBHTbο6ηηηημ o6pa3OM, HanpHMep, nyTeM ocaatfleHHH coJWHoft KHCJioToň b xanecTBe ranpo-XJIOpHna, ΠρΗΗβΜ H6T Heo6XOnHMOCTH paĎOTaTb B 6e3BOnHWX yCJIOBHHX. Πρκ 3T0M UaCTbηβτρηη, H3 xjiopaMHHa T, ocaxnaéTCH b KanecTBe xjiopHCToro Harpna, yjiynmaa peraa-ioiuhm o6pa3OM $HJibTpyeMOCTb nponyKTa. Πρη naJibHeftmeň o6pa6oTKe, HanpHMep, H3-BeCTHblM cnOCOfíOM nerHňPaTaiIHH C φΤΟρΗΟΤΜΜ BOnOponOM B 1 la-XJIOp-MeTanHKJlHH,xjiopHCTHft HaTpnň He MémaeT, nojiyna»T Bbixon 11 a—xjiop—MeTanHKJiHHa nopHnKa * 95%TeopHH. H3oRpeTeHne ofíbHCHaeTca Ha cnenywmHX npHMepax nonpo6Hee. IIpHMep 1 6,25 κγ (12,5 moji) rnnpoxnopHna 5-rHnpOKCH~TeTpaiiHKJiHHa pacTBopaioT hjih cyc-neHnHpywT b CMecH 5,5 ji BonH H 30 a aneTOHa, CMecb oxjiaxnaioT no TeMnepaTypbi-30 - -40°C. BbicTpo npHOaBJíjnoT (b Tenemie 1-2 MHHyT) 4,25 κγ (15 moji) xjiop-aMHHa T h nonojiHHTejibHO nepeMemHBawT b TeneHHe 5-6 MHHyT. Πρκ BO3pacTaHHHTeMnepaTypbi no -15.,.-10°C oGpasyeTCH ποητη, npospaHHbiň acejiTbiň pacTBop. npH6aB-neHHeM CMecH H3 87,5 ji aneTOHa h 2,25 ji KOHneHTpupoBaHHoň cojihhoh khcjioth,npenBapHTejibHO oxjiaxneaHoň n° 0 ” +5°C, ocaxnaioT nponyKT peaKiiHH. flonojiflHTejibHO;nepeMeiiHBaioT b TeneHHe 1 naca npH 18 - 20®C h b TeneHHe 1,5 naca npn -5 no I-10°C, φκπΒτρνιοτ, npoMMBawT aneTOHOM h cyrnať. nojiynaioT 6,9 κγ 1 la-xjiop-5-rHnpoKCHTeTpanHKJiHH-6,12-reMHKeTajib-rHnpoxjiopHn-nwrnnpaTa c conepxaHHeM NaCl οκοπο 14%, αοοτΒβτοτΒβΗΗΟ 5,93 κγ ηηοτογο nponyKTa f(83% TeopHH). 2Ό T.nn.: 212 —216 (pasn.), - 22,5°C (c = 1, MeTaHon c 1% HCl) b nepecneTe HaNaCl- h ReaBonHoe semecTBO. nponyKT He HMeeT HK nonocw Bwne 1666 cm_í , hto CBHfleTenhCTByeT 06 otcvtctbhh
HexenaTenbHoft κβτοφορΜΜ. ngHMej>_2 C ΤβΜ, HTOOM nOKasaTb ΒΠΗΗΗΗβ paŠnHHHbiX KOJItmeCTB CpenCTB XnopHpoBaHHH npHMepnOBTOpHJIH C pasnHHHHMH ΚΟΠΗΗβΟΤΒΒΜΗ XJIOpaMHHa T. 251657 4 riojiyHeHbí cjienywimie pe3yjn>TaTbi:
moji xnopAMHHa T/moji OTU
Bwxofl reMHKeTann 1 40% 1,4 ' 70% 1,6 54% ΠρΗΜβρ 3 ΠΟΒΤΟΡΚΠΗ ΠρΗΜβρ 1 , OflHaKO BM6CTO OKCHTeTpaiIHKJIHH-rHApOXJIOpH.ria HCnOJIb3y»T ORCH~TeTpaiíHKJIHH-flHrHflpaT BMeCTe CO CTeXHOMtíTpHHeCKHM KOJIHHeCTBOM COJIHHOň KHCJ10TM.nojiynawT 63,6% (.τβορΗκ) 1 la—xJiopoKCHTeTpaijHKJiHH—reMHKeTajia·
ΦΟΡΜΥΠΑ H30RPETEHHU 1. CnocoC πο,πγηβΗΗΒ 1 la-xjiop-5-FHflppKCHTeTpaiiHKjiHH-6,12-reMHKeTajia nyTeM ;XJlOpupOBaHHH ΟΚΟΗΤβΤρβμΗΚΠΗΗβ B CMeiDHBaiOmeMCH C BOflOň paCTBOpHTejie ΠρΗ ΤβΜΠβ*paTypax b npenejiax -40 - +5°C, H H3OJiHpoBaHHH προπγκτβ peaKtiHH nyTeM ocaamemijí,oTjiHMaraimtíicH τβΜ, ητο b KanecTSe cpencTBa xjiopHpoBaHHH Hcnojib3yioT mejionHyw COJlfeΝ-μοήοχλο papnricyjih<í>OHaMHfla. 2. Cnoco6 no nyHRTy 1, OTJiHnawnmftcH τβΜ, hto ^ejionnyio conb - Monoxjiop-apHn-cyjib$OHaMH^a Hcnojib3ywT b KOJiHnecTse 1-1,6 moji, πρβπποΗΤΗΤβπΒΗο 1,2-1,3 moji :Ha moji OKCHTeTpanHKjiHHa. 3. Cnocofí no nyHKTy 1 ,OTJinHaK>mnňcH τβΜ, πτο b KanecTBe menoMHoň cojih N-moho*xjiop-apitncyjibftoHaMH/ia Hcnojib3ywT N-MOHOxjiop-ii-Tonyojicyjib^HaMHflHbiň naTpHň. 4. Cnoco6 no nyHKTy 1, oTjnniawnmHCJi .τβΜ, πτο peaKima npoBOflHTCH np« 3HaneHHHpH ot 5 p;o 6,5, npeflnouTHTejibHO 5,5 no 6.
AHHOTAUHH
Cnocó6 nojiyneHHH 1 l{i-xnop-5-rHflOKCH-TeTpanHKJiHH-6,12-reMHKeTajni Η3θ6ρβτβΗΗβ KacaeTca cnocoĎa nojiyneHHH 1 ía-xJiop-5-rHflpoKCHTeTpauHKJiHH-6,12-reMtíKeTajiH nyTeM xjiopHpoBaHHH 5-rnflpoKCHTeTpauHKJinHa.
UeJIbW Η3θ6ρβΤβΗΗΗ HBJIHeTCH CHOCO6 npOCTOft B ΤβΧΗΟΠΟΓΗΗβΟΚΟΜ ΟΤΗΟΙΠβΗΗΗ H HC"nojib3y»nptó 6ojiee nemeBoe cpeflCTBO χιιορκροΒβΗΗΛ no cpaBHeHmo c N-xjiopcyKijHHHMH-flOM. Bbino HaňfleHo, hto njejionHbie cojih N-MOHoxJiop-apHJicyjih<i>oHaMHflOB hbjuhotchOTJIHHHMMH CpeflCTBaMH flJIH ΧΠΟρΗρΟΒβΗΗΗ S—rHflpOXCH“ΤβΤρ,ΗΠΗΚΙΙΗΗΗ B ΠΟΙΙΟΜβΗΗΗ 11ac o6pa3OBaHHeM 6,12-reMHKeTajiH b 3HOJibHoň φσρΜβ. ÍIpH3HaHo Η3θβρβτβΗΗβΜ no pe3yjibTaTaM 3KcnepyH3H, ocymecTBJíeHHoň Betonetbomno fleJiaM Η3θ6ρβτβΗΗΑ η πβτβΗΤΟΒ TUP. 251657
Claims (4)
- 5 pRbdmSt vynálezu1. Způsob přípravy IIa-chlor~5-hyaroxyťetracyklin-6,12-hemiketalu chloraci pxytetracyklinu v rozpouštědle mísi-telmém s vodou, při teplotách v rozmezí -40 až + 5θ °C,a izolací reakčniho produktu sedimentací, vyznačující setím, že se jako chlorační prostředek používá alkalickásůl N-monochlorarylsulfonamidu.
- 2. Způsob podle bodu 1, vyznačující se tím, že alaklickásůl N~monochlorarylsulfonamidu se používá v množství 1 až 1,6 mol, výhodně 1,2 až 1,5 mol na mol oxytetracyklínu.
- 5. Způsob podle bodu 1, vyznačující se tím, že jako alka-lická sůl N-monoohlor-arylsulfonamidu se používá sodnásůl N-mobochlor-p-toluensulfonamidu.
- 4. Způsob podle bodu 1, vyznačující se tím, že se reakceprovádí při hodnotě pH od 5 do 6, výhodně 5,5 až 6. 251657
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DD24273682A DD219021A3 (de) | 1982-08-24 | 1982-08-24 | Verfahren zur herstellung von 11a-chlor-5-hydroxy-tetracyclin-6,12-hemiketal |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CS352483A1 CS352483A1 (en) | 1985-07-16 |
| CS251657B1 true CS251657B1 (en) | 1987-07-16 |
Family
ID=5540820
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CS833524A CS251657B1 (en) | 1982-08-24 | 1983-05-19 | Preparation method of the 11a-chlorine-5-hydroxytetracyclone-6,12-hemiketale |
Country Status (2)
| Country | Link |
|---|---|
| CS (1) | CS251657B1 (cs) |
| DD (1) | DD219021A3 (cs) |
-
1982
- 1982-08-24 DD DD24273682A patent/DD219021A3/de not_active IP Right Cessation
-
1983
- 1983-05-19 CS CS833524A patent/CS251657B1/cs unknown
Also Published As
| Publication number | Publication date |
|---|---|
| DD219021A3 (de) | 1985-02-20 |
| CS352483A1 (en) | 1985-07-16 |
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