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【结 构 式】

【分子编号】16192

【品名】methyl (2S)-2-(1-benzothiophen-5-yl)-3-(tetrahydro-2H-pyran-2-yloxy)propanoate

【CA登记号】

【 分 子 式 】C17H20O4S

【 分 子 量 】320.4094

【元素组成】C 63.73% H 6.29% O 19.97% S 10.01%

与该中间体有关的原料药合成路线共 1 条

合成路线1

该中间体在本合成路线中的序号:(XV)

2) The condensation of aldehyde (IV) with bromoform by means of LiOH in hot dioxane/water gives (±)-2-(benzo[b]thiophen-5-yl)-2-hydroxyacetic acid (XI), which is submitted to optical resolution by fractional crystallization of its 2(R)-aminobutanol salt in isopropanol and acidification with HCl to yield (R)-(-)-2-(benzo[b]thiophen-5-yl)-2-hydroxyacetic acid (XII). The cyclization of (XII) with acetone and concentrated H2SO4 affords (R)-(-)-5-(benzo[b]thiophen-5-yl)-2,2-dimethyl-1,3-dioxolan-4-one (XIII), which, by treatment with methanol and H2SO4, is converted into (R)-(-)-2-(benzo[b]thiophen-5-yl)-2-hydroxyacetic acid methyl ester (XIV). The protection of the OH group of (XIV) with dihydropyran (DHP) and pyridinium p-toluenesulfonate (Pyr·TsOH) affords the corresponding tetrahydropyranyl ether (XV), which is reduced with NaBH4 in ethanol, giving (R)-(-)-2-(benzo[b]thiophen-5-yl)-2-(tetrahydropyranyloxy)ethanol (XVI). Finally, this compound is condensed with 2-(diethylamino)ethyl chloride (XVII) by means of NaOH and tetrabutylammonium hydrogensulfate in toluene/water, followed by acidification with HCl. 3) The (R)-dioxolane (XIII) can also be obtained as follows: The racemic hydroxyacetic acid (XI) is cyclized with acetone and H2SO4 as before, giving the racemic dioxolane (XVIII). This compound is dissolved in hot (50 C) tert-amyl alcohol along with 1,8-diazabicyclo[5.4.0]-7-undecene (DCU); this solution is then seeded with a suspension of the (R)-(-)-isomer (XIII) in the same solvent and is slowly cooled at 25 C; a 81% yield of pure crystals of (R)-(-)-isomer (XIII) is obtained. This procedure allows for improving the yields by recovering the unused (S)-(+)-isomer.

1 Martel, A.M.; Prous, J.; Castaner, J.; T-588. Drugs Fut 1997, 22, 4, 386.
2 Nakano, J.; Taya, N.; Chaki, H.; Yamafuji, T.; Momonoi, K. (Toyama Chemical Co., Ltd.); Benzo b thiophen-5-yl deriv. and process for producing the same. EP 0565965 .
中间体序号 中间体编号 品名 CAS号 分子式 供应商 用于合成
48572 (S)-(+)-2-Amino-1-butanol; L-(+)-2-Amino-1-butanol; (S)-2-Amino-1-butanol 5856-62-2 C4H11NO 详情 详情
(IV) 16181 1-benzothiophene-5-carbaldehyde C9H6OS 详情 详情
(XI) 16188 2-(1-benzothiophen-5-yl)-2-hydroxyacetic acid C10H8O3S 详情 详情
(XII) 16189 (2R)-2-(1-benzothiophen-5-yl)-2-hydroxyethanoic acid C10H8O3S 详情 详情
(XIII) 16190 (5R)-5-(1-benzothiophen-5-yl)-2,2-dimethyl-1,3-dioxolan-4-one C13H12O3S 详情 详情
(XIV) 16191 methyl (2R)-2-(1-benzothiophen-5-yl)-2-hydroxyethanoate C11H10O3S 详情 详情
(XV) 16192 methyl (2S)-2-(1-benzothiophen-5-yl)-3-(tetrahydro-2H-pyran-2-yloxy)propanoate C17H20O4S 详情 详情
(XVI) 16193 (2R)-2-(1-benzothiophen-5-yl)-3-(tetrahydro-2H-pyran-2-yloxy)-1-propanol C16H20O3S 详情 详情
(XVII) 16194 2-chloro-N,N-diethyl-1-ethanamine; N-(2-chloroethyl)-N,N-diethylamine 100-35-6 C6H14ClN 详情 详情
(XVIII) 16195 5-(1-benzothiophen-5-yl)-2,2-dimethyl-1,3-dioxolan-4-one C13H12O3S 详情 详情
Extended Information