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【结 构 式】 
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【分子编号】65130 【品名】(3R,4S)-1-benzyl-3-({[tert-butyl(dimethyl)silyl]oxy}methyl)-4-(3-fluorophenyl)pyrrolidine; [(3R,4S)-1-benzyl-4-(3-fluorophenyl)pyrrolidinyl]methyl tert-butyl(dimethyl)silyl ether 【CA登记号】 |
【 分 子 式 】C24H34FNOSi 【 分 子 量 】399.6240032 【元素组成】C 72.13% H 8.58% F 4.75% N 3.5% O 4% Si 7.03% |
合成路线1
该中间体在本合成路线中的序号：(VIII)m-Fluorocinnamic acid (I) is coupled to (S)-4-benzyloxazolidin-2-one (II), via the corresponding mixed anhydride with pivaloyl chloride, to furnish the N-cinnamoyl oxazolidinone (III). Cycloaddition of (III) with N-methoxymethyl-N-trimethylsilylmethyl benzylamine (IV) in the presence of trifluoroacetic acid produces a mixture of the diastereoisomeric pyrrolidines (V) and (VI), separable by column chromatography. The desired isomer (V) is then reduced by means of LiAlH4 to the primary alcohol (VII), which is further protected by silylation with t-butyldimethylsilyl chloride. The resultant silyl ether (VIII) is then subjected to benzyl group cleavage under transfer hydrogenation conditions, producing pyrrolidine (IX) (1).
| 【1】 Mills, S.G.; Kim, D.; Hale, J.; MacCoss, M.; Berk, S.; Chapman, K.; Lynch, C.; Caldwell, C.; Willoughby, C.; Rosauer, K. (Merck & Co., Inc.); Pyrrolidine modulators of chemokine receptor activity. US 6265434; WO 0059503 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (I) | 63980 | m-Fluorocinnamic acid; (E)-3-(3-fluorophenyl)-2-propenoic acid | C9H7FO2 | 详情 | 详情 | |
| (II) | 25351 | (4R)-4-benzyl-1,3-oxazolidin-2-one; (R)-(+)-4-benzyl-2-oxazolidinone | 102029-44-7 | C10H11NO2 | 详情 | 详情 |
| (III) | 63983 | (4S)-4-benzyl-3-[(E)-3-(3-fluorophenyl)-2-propenoyl]-1,3-oxazolidin-2-one | C19H16FNO3 | 详情 | 详情 | |
| (IV) | 25556 | N-benzyl-N-(methoxymethyl)-N-[(trimethylsilyl)methyl]amine; N-benzyl-N-(methoxymethyl)(trimethylsilyl)methanamine | 1871-96-1 | C13H23NOSi | 详情 | 详情 |
| (V) | 63985 | (4S)-4-benzyl-3-{[(3R,4S)-1-benzyl-4-(3-fluorophenyl)pyrrolidinyl]carbonyl}-1,3-oxazolidin-2-one | C28H27FN2O3 | 详情 | 详情 | |
| (VI) | 63984 | (4S)-4-benzyl-3-{[(3S,4R)-1-benzyl-4-(3-fluorophenyl)pyrrolidinyl]carbonyl}-1,3-oxazolidin-2-one | C28H27FN2O3 | 详情 | 详情 | |
| (VII) | 63986 | [(3R,4S)-1-benzyl-4-(3-fluorophenyl)pyrrolidinyl]methanol | C18H20FNO | 详情 | 详情 | |
| (VIII) | 65130 | (3R,4S)-1-benzyl-3-({[tert-butyl(dimethyl)silyl]oxy}methyl)-4-(3-fluorophenyl)pyrrolidine; [(3R,4S)-1-benzyl-4-(3-fluorophenyl)pyrrolidinyl]methyl tert-butyl(dimethyl)silyl ether | C24H34FNOSi | 详情 | 详情 | |
| (IX) | 63988 | (3R,4S)-3-({[tert-butyl(dimethyl)silyl]oxy}methyl)-4-(3-fluorophenyl)pyrrolidine; tert-butyl(dimethyl)silyl [(3R,4S)-4-(3-fluorophenyl)pyrrolidinyl]methyl ether | C17H28FNOSi | 详情 | 详情 |