【结 构 式】 |
【分子编号】58246 【品名】(2S)-2-hexyl-4-pentenoic acid 【CA登记号】 |
【 分 子 式 】C11H20O2 【 分 子 量 】184.2786 【元素组成】C 71.7% H 10.94% O 17.36% |
合成路线1
该中间体在本合成路线中的序号:(VII)The acylation of (-)-2,10-camphorsultam (II) with octanoyl chloride (I) provides the N-octanoyl sultam (III). Diastereoselective alkylation of the lithium enolate of (III) with allyl bromide (IV) gives rise to the (2S)-2-propenoyloctanoyl sultam (V). Hydrolysis of the N-acyl sultam (V) to furnish acid (VI) is then effected by treatment with hydrogen peroxide-tetrabutylammonium hydroxide. Finally, catalytic hydrogenation of the unsaturated acid (VI) in the presence of either Pd/C or Pt/C yields the required (R)-2-propyloctanoic acid. Alternatively, the title compound is obtained by hydrogenation of the N-acyl sultam (V) to the saturated derivative (VII), followed by hydrolytic removal of the camphorsultam moiety.
【1】 Hasegawa, T.; Kawanaka, Y.; Kasamatsu, E.; Iguchi, Y.; Yonekawa, Y.; Okamoto, M.; Ohta, C.; Hashimoto, S.; Ohuchida, S.; Process development of ONO-2506: A therapeutic agent for stroke and Alzheimer's disease. Org Process Res Dev 2003, 7, 2, 168. |
【2】 Hasegawa, T.; Yamamoto, H.; A practical synthesis of optically active (R)-2-propyloctanoic acid: Therapeutic agent for Alzheimer's disease. Bull Chem Soc Jpn 2000, 73, 2, 423. |
【3】 Hasegawa, T.; Yamamoto, H.; A practical removal method of camphorsultam. Synlett 1998, 8, 882. |
【4】 Yamamoto, H. (Ono Pharmaceutical Co., Ltd.); Novel intermediates and processes for the preparation of optically active octanoic acid derivs.. EP 1078921; US 6333415; WO 9958513 . |
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) | 11123 | Octanoyl chloride; n-Caprylyl chloride;Capryloyl chloride | 111-64-8 | C8H15ClO | 详情 | 详情 |
(II) | 58242 | (1S,5R,7R)-10,10-dimethyl-3lambda~6~-thia-4-azatricyclo[5.2.1.0~1,5~]decane-3,3-dione | C10H17NO2S | 详情 | 详情 | |
(III) | 58243 | (1S,5R,7R)-10,10-dimethyl-4-octanoyl-3lambda~6~-thia-4-azatricyclo[5.2.1.0~1,5~]decane-3,3-dione | C18H31NO3S | 详情 | 详情 | |
(IV) | 11463 | 3-Bromo-1-propene; 3-Bromopropene;allyl bromide | 106-95-6 | C3H5Br | 详情 | 详情 |
(V) | 58244 | (1S,5R,7R)-4-[(2S)-2-hexyl-4-pentenoyl]-10,10-dimethyl-3lambda~6~-thia-4-azatricyclo[5.2.1.0~1,5~]decane-3,3-dione | C21H35NO3S | 详情 | 详情 | |
(VI) | 58245 | (1S,5R,7R)-10,10-dimethyl-4-[(2R)-2-propyloctanoyl]-3lambda~6~-thia-4-azatricyclo[5.2.1.0~1,5~]decane-3,3-dione | C21H37NO3S | 详情 | 详情 | |
(VII) | 58246 | (2S)-2-hexyl-4-pentenoic acid | C11H20O2 | 详情 | 详情 |