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【结 构 式】 
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【分子编号】38424 【品名】(2S)-Spiro[benzo[C]thiophene-1(3H),4'-piperidine]-1'-carboxylic acid, 1,1-dimethylethyl ester, 2-oxide 【CA登记号】191673-21-9 |
【 分 子 式 】C17H23NO3S 【 分 子 量 】321.44056 【元素组成】C 63.52% H 7.21% N 4.36% O 14.93% S 9.98% |
合成路线1
该中间体在本合成路线中的序号：(V)Lithiation of 2-bromobenzyl thiol (I) followed by addition to N-Boc-4-piperidone (II) gave mercapto alcohol (III), which was cyclized to the spiro derivative by refluxing in 4N sulfuric acid. Protection as the tert-butyl carbamate (IV), followed by oxidation with m-chloroperbenzoic acid produced sulfoxide (V). After acid cleavage of the Boc protecting group of (V), resolution with (S)-(+)-mandelic acid furnished the required (S)-enantiomer (VII). Alternatively, asymmetric oxidation of sulfide (IV) with (3'S,2R)-(-)-N-(phenylsulfonyl)(3,3-dichlorocamphoryl)oxaziridine produced the (S)-sulfoxide (VI), which was further deprotected to (VII) with HCl in dioxan.
| 【1】 Kurata, H.; Ito, K.; Nakajima, K.; Yamaguchi, T.; Ishibashi, K.; Fukuzawa, T.; Nishi, T. (Sankyo Co., Ltd.); Azaheterocyclic cpds. having tachykinin receptor antagonist activity; NK1 and NK2. EP 0776893; JP 1998152478; JP 1998182649; JP 1998182650 . |
| 【2】 Nishi, T.; Yamaguchi, T. (Sankyo Co., Ltd.); Salts of optically active sulfoxide deriv.. EP 0987269; JP 1999043490; WO 9854191 . |
| 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) | 38421 | (2-bromophenyl)methanethiol; 2-bromobenzylhydrosulfide | C7H7BrS | 详情 | 详情 | |
| (II) | 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 |
| (III) | 38422 | tert-butyl 4-hydroxy-4-[2-(sulfanylmethyl)phenyl]-1-piperidinecarboxylate | C17H25NO3S | 详情 | 详情 | |
| (IV) | 38423 | Spiro[benzo[C]thiophene-1(3H),4'-piperidine]-1'-carboxylic acid, 1,1-dimethylethyl ester | 173944-03-1 | C17H23NO2S | 详情 | 详情 |
| (V) | 38424 | (2S)-Spiro[benzo[C]thiophene-1(3H),4'-piperidine]-1'-carboxylic acid, 1,1-dimethylethyl ester, 2-oxide | 191673-21-9 | C17H23NO3S | 详情 | 详情 |
| (VI) | 38425 | Spiro[benzo[C]thiophene-1(3H),4'-piperidine]-1'-carboxylic acid, 1,1-dimethylethyl ester, 2-oxide | 173944-04-2 | C17H23NO3S | 详情 | 详情 |
| (VII) | 38426 | (2S)-Spiro[benzo[C]thiophene-1(3H),4'-piperidine] 2-oxide | 191673-15-1 | C12H15NOS | 详情 | 详情 |