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【结 构 式】 
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【分子编号】61348 【品名】methyl (3R)-3-{[(4R)-4-benzyl-2-oxo-1,3-oxazolidin-3-yl]carbonyl}-5-cyanopentanoate 【CA登记号】 |
【 分 子 式 】C18H20N2O5 【 分 子 量 】344.36728 【元素组成】C 62.78% H 5.85% N 8.13% O 23.23% |
合成路线1
该中间体在本合成路线中的序号：(XVIII)3-(Carbomethoxy)propionyl chloride (XV) is condensed with the chiral oxazolidine (XVI) to provide (XVII). Titanium-catalyzed Michael addition of acrylonitrile to the N-acyl oxazolidine (XVII) affords nitrile (XVIII), which is reduced to the primary amine (XIX) by catalytic hydrogenation in the presence of PtO2. Reductive alkylation of amine (XIX) with N-Boc-4-piperidone (XX) gives rise to the aminopiperidine (XXI). This is then cyclized to the piperidinyl piperidone (XXII) upon heating in acetonitrile. After alkaline hydrolysis of the methyl ester group of (XXII), coupling of the resultant acid (XXIII) with methylamine gives rise to the corresponding amide (XXIV). The N-Boc protecting group of (XXIV) is then removed by treatment with trifluoroacetic acid to furnish piperidine (XXV)
| 【1】 Carruthers, N.I.; Alaimo, C.A.; Shih, N.-Y.; Lavey, B.J.; Ting, P.C.; Reichard, G.A. (Schering Corp.); Substd. oximes as neurokinin antagonists. EP 1032561; WO 9926924 . |
| 【2】 Carruthers, N.I.; Reichard, G.A.; Shih, N.-Y.; Lavey, B.J.; Alaimo, C.A.; Ting, P.C. (Schering Corp.); Substd. oximes as neurokinin antagonists. US 6063926 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (A) | 10847 | Acrylonitrile | 107-13-1 | C3H3N | 详情 | 详情 |
| (XV) | 18060 | 4-Chloro-4-oxobutyric acid methyl ester; 3-Carbomethosypropionyl chloride; Methyl 4-chloro-4-oxobutanoate | 1490-25-1 | C5H7ClO3 | 详情 | 详情 |
| (XVI) | 25351 | (4R)-4-benzyl-1,3-oxazolidin-2-one; (R)-(+)-4-benzyl-2-oxazolidinone | 102029-44-7 | C10H11NO2 | 详情 | 详情 |
| (XVII) | 61347 | methyl 4-[(4R)-4-benzyl-2-oxo-1,3-oxazolidin-3-yl]-4-oxobutanoate | C15H17NO5 | 详情 | 详情 | |
| (XVIII) | 61348 | methyl (3R)-3-{[(4R)-4-benzyl-2-oxo-1,3-oxazolidin-3-yl]carbonyl}-5-cyanopentanoate | C18H20N2O5 | 详情 | 详情 | |
| (XIX) | 61349 | methyl (3R)-6-amino-3-{[(4R)-4-benzyl-2-oxo-1,3-oxazolidin-3-yl]carbonyl}hexanoate | C18H24N2O5 | 详情 | 详情 | |
| (XX) | 18620 | tert-butyl 4-oxo-1-piperidinecarboxylate;BOC-Piperidone;N-(tert-Butoxycarbonyl)-4-piperidone; N-Boc-4-piperidone | 79099-07-3 | C10H17NO3 | 详情 | 详情 |
| (XXI) | 61350 | tert-butyl 4-[((4R)-4-{[(4R)-4-benzyl-2-oxo-1,3-oxazolidin-3-yl]carbonyl}-6-methoxy-6-oxohexyl)amino]-1-piperidinecarboxylate | C28H41N3O7 | 详情 | 详情 | |
| (XXII) | 61351 | C18H30N2O5 | 详情 | 详情 | ||
| (XXIII) | 61352 | C17H28N2O5 | 详情 | 详情 | ||
| (XXIV) | 61353 | C18H31N3O4 | 详情 | 详情 | ||
| (XXV) | 61354 | C13H23N3O2 | 详情 | 详情 |