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【结 构 式】 
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【分子编号】27580 【品名】(4S,5S)-4-(methoxymethyl)-2-methyl-5-[4-(methylsulfanyl)phenyl]-4,5-dihydro-1,3-oxazole 【CA登记号】 |
【 分 子 式 】C13H17NO2S 【 分 子 量 】251.34952 【元素组成】C 62.12% H 6.82% N 5.57% O 12.73% S 12.76% |
合成路线1
该中间体在本合成路线中的序号：(XXXV)In a related procedure, chiral oxazoline (XXXV) was prepared by condensation of ethyl acetimidate (XXXIII) with (S,S)-thiomicamine (XXXII), followed by O-methylation with MeI and sodium tert-pentoxide. Condensation of the lithium salt of (XXXV) with diethylchlorophosphate at -78 C provided phosphonate (XXXVI), which was submitted to a Horner-Emmons reaction with pyridine aldehyde (XV) to yield the vinyl oxazoline (XXXVII). Conjugate addition of the organolithium reagent (XXXVIII) to (XXXVII) then produced adduct (XXXIX) as the major diastereoisomer. Hydrolysis of the oxazoline of (XXXIX) upon refluxing in isopropyl alcohol with H2SO4 yielded isopropyl ester (XL). Pyridine carboxylate (XLI) was further obtained by carbonylation of (XL) under atmosphere of CO in the presence of bis(diphenylphosphino)ferrocene and palladium diacetate in MeOH.
| 【1】 Frey, L.F.; Devine, P.N.; Tschaen, D.M.; Dolling, U.H.; Tillyer, R.D.; Kato, Y. (Banyu Pharmaceutical Co., Ltd.; Merck & Co., Inc.); Stereoselective deoxygenation reaction. EP 0923557; JP 1999514676; WO 9806700 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (XV) | 27563 | 2-bromo-6-butylnicotinaldehyde | C10H12BrNO | 详情 | 详情 | |
| (XXXII) | 27578 | (1S,2S)-2-amino-1-[4-(methylsulfanyl)phenyl]-1,3-propanediol | C10H15NO2S | 详情 | 详情 | |
| (XXXIII) | 12831 | ethyl ethanimidoate | 1000-84-6 | C4H9NO | 详情 | 详情 |
| (XXXIV) | 27579 | [(4S,5S)-2-methyl-5-[4-(methylsulfanyl)phenyl]-4,5-dihydro-1,3-oxazol-4-yl]methanol | C12H15NO2S | 详情 | 详情 | |
| (XXXV) | 27580 | (4S,5S)-4-(methoxymethyl)-2-methyl-5-[4-(methylsulfanyl)phenyl]-4,5-dihydro-1,3-oxazole | C13H17NO2S | 详情 | 详情 | |
| (XXXVI) | 27581 | diethyl [(4S,5S)-4-(methoxymethyl)-5-[4-(methylsulfanyl)phenyl]-4,5-dihydro-1,3-oxazol-2-yl]methylphosphonate | C17H26NO5PS | 详情 | 详情 | |
| (XXXVII) | 27582 | 2-bromo-6-butyl-3-((E)-2-[(4S,5S)-4-(methoxymethyl)-5-[4-(methylsulfanyl)phenyl]-4,5-dihydro-1,3-oxazol-2-yl]ethenyl)pyridine | C23H27BrN2O2S | 详情 | 详情 | |
| (XXXVIII) | 27583 | 1,3-benzodioxol-5-yllithium | C7H5LiO2 | 详情 | 详情 | |
| (XXXIX) | 27584 | [(4S,5S)-2-[(2S)-2-(1,3-benzodioxol-5-yl)-2-(2-bromo-6-butyl-3-pyridinyl)ethyl]-5-[4-(methylsulfanyl)phenyl]-4,5-dihydro-1,3-oxazol-4-yl]methyl methyl ether | C30H33BrN2O4S | 详情 | 详情 | |
| (XL) | 27585 | isopropyl (3S)-3-(1,3-benzodioxol-5-yl)-3-(2-bromo-6-butyl-3-pyridinyl)propanoate | C22H26BrNO4 | 详情 | 详情 | |
| (XLI) | 27586 | methyl 3-[(1S)-1-(1,3-benzodioxol-5-yl)-3-isopropoxy-3-oxopropyl]-6-butyl-2-pyridinecarboxylate | C24H29NO6 | 详情 | 详情 |