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【结 构 式】

【分子编号】62445

【品名】(1S,2R)-2-phenylcyclohexyl 2-chloroacetate

【CA登记号】

【 分 子 式 】C14H17ClO2

【 分 子 量 】252.74048

【元素组成】C 66.53% H 6.78% Cl 14.03% O 12.66%

与该中间体有关的原料药合成路线共 3 条

合成路线1

该中间体在本合成路线中的序号:(XXV)

Addition of phenylmagnesium bromide to cyclohexene oxide (XXI) in the presence of CuCl gave trans-2-phenylcyclohexanol (XXII), which was further esterified with chloroacetyl chloride to afford 2-phenylcyclohexyl chloroacetate (XXIII). Enantioselective hydrolysis of the racemic ester (XXIII) by means of Pseudomonas fluorescens lipase provided pure (1R,2S)-2-phenylcyclohexanol (XXIV), which was again esterified with chloroacetyl chloride, yielding the chiral ester (XXVI). Darzen's condensation of chloro ester (XXVI) with anisaldehyde (X) led to the chiral glycidic ester (XXVII). Epoxide ring opening in (XXVII) with 2-aminothiophenol (VII) furnished amino ester (XXVIII). Intermediate thiazepinone (VIII) was then obtained by cyclization of (XXVIII) using p-toluenesulfonic acid in refluxing xylene. Alternatively, amino ester (XXVIII) was first hydrolyzed to amino acid (XXIX), which was subsequently cyclized with p-toluenesulfonic acid as above (11). The final cyclization of amino acid (XXIX) to the intermediate thiazepinone (VIII) has also been carried out in the presence of trichloroacetic acid

1 Plaum, M.J.M.; Boesten, W.H.J.; Process for the preparation of a benzothiazepine. EP 0796853; JP 1998007667; US 5859241 .
中间体序号 中间体编号 品名 CAS号 分子式 供应商 用于合成
(+/-)-(XXII) 51208 (1R,2S)-2-phenylcyclohexanol C12H16O 详情 详情
(+/-)-(XXIII) 62445 (1S,2R)-2-phenylcyclohexyl 2-chloroacetate C14H17ClO2 详情 详情
(VII) 25182 2-aminobenzenethiol 137-07-5 C6H7NS 详情 详情
(VIII) 62436 (2S,3S)-3-hydroxy-2-(4-methoxyphenyl)-2,3-dihydro-1,5-benzothiazepin-4(5H)-one C16H15NO3S 详情 详情
(X) 27251 4-methoxybenzaldehyde; Anisicaldehyde; p-anisaldehyde 123-11-5 C8H8O2 详情 详情
(XXI) 17986 7-oxabicyclo[4.1.0]heptane; cyclohexene oxide 286-20-4 C6H10O 详情 详情
(XXIV) 10492 (1S,2R)-(+)-trans-2-Phenyl-1-cyclohexanol; (1S,2R)-2-Phenylcyclohexanol 2362-61-0 C12H16O 详情 详情
(XXV) 62445 (1S,2R)-2-phenylcyclohexyl 2-chloroacetate C14H17ClO2 详情 详情
(XXVI) 62445 (1S,2R)-2-phenylcyclohexyl 2-chloroacetate C14H17ClO2 详情 详情
(XXVII) 62446 (1R,2S)-2-phenylcyclohexyl (2R,3S)-3-(4-methoxyphenyl)-2-oxiranecarboxylate C22H24O4 详情 详情
(XXVIII) 62447 (1R,2S)-2-phenylcyclohexyl (2S,3S)-3-[(2-aminophenyl)sulfanyl]-2-hydroxy-3-(4-methoxyphenyl)propanoate C28H31NO4S 详情 详情
(XXIX) 62448 (2S,3S)-3-[(2-aminophenyl)sulfanyl]-2-hydroxy-3-(4-methoxyphenyl)propanoic acid C16H17NO4S 详情 详情

合成路线2

该中间体在本合成路线中的序号:(XXVI)

Addition of phenylmagnesium bromide to cyclohexene oxide (XXI) in the presence of CuCl gave trans-2-phenylcyclohexanol (XXII), which was further esterified with chloroacetyl chloride to afford 2-phenylcyclohexyl chloroacetate (XXIII). Enantioselective hydrolysis of the racemic ester (XXIII) by means of Pseudomonas fluorescens lipase provided pure (1R,2S)-2-phenylcyclohexanol (XXIV), which was again esterified with chloroacetyl chloride, yielding the chiral ester (XXVI). Darzen's condensation of chloro ester (XXVI) with anisaldehyde (X) led to the chiral glycidic ester (XXVII). Epoxide ring opening in (XXVII) with 2-aminothiophenol (VII) furnished amino ester (XXVIII). Intermediate thiazepinone (VIII) was then obtained by cyclization of (XXVIII) using p-toluenesulfonic acid in refluxing xylene. Alternatively, amino ester (XXVIII) was first hydrolyzed to amino acid (XXIX), which was subsequently cyclized with p-toluenesulfonic acid as above (11). The final cyclization of amino acid (XXIX) to the intermediate thiazepinone (VIII) has also been carried out in the presence of trichloroacetic acid

1 Plaum, M.J.M.; Boesten, W.H.J.; Process for the preparation of a benzothiazepine. EP 0796853; JP 1998007667; US 5859241 .
中间体序号 中间体编号 品名 CAS号 分子式 供应商 用于合成
(+/-)-(XXII) 51208 (1R,2S)-2-phenylcyclohexanol C12H16O 详情 详情
(+/-)-(XXIII) 62445 (1S,2R)-2-phenylcyclohexyl 2-chloroacetate C14H17ClO2 详情 详情
(VII) 25182 2-aminobenzenethiol 137-07-5 C6H7NS 详情 详情
(VIII) 62436 (2S,3S)-3-hydroxy-2-(4-methoxyphenyl)-2,3-dihydro-1,5-benzothiazepin-4(5H)-one C16H15NO3S 详情 详情
(X) 27251 4-methoxybenzaldehyde; Anisicaldehyde; p-anisaldehyde 123-11-5 C8H8O2 详情 详情
(XXI) 17986 7-oxabicyclo[4.1.0]heptane; cyclohexene oxide 286-20-4 C6H10O 详情 详情
(XXIV) 10492 (1S,2R)-(+)-trans-2-Phenyl-1-cyclohexanol; (1S,2R)-2-Phenylcyclohexanol 2362-61-0 C12H16O 详情 详情
(XXV) 62445 (1S,2R)-2-phenylcyclohexyl 2-chloroacetate C14H17ClO2 详情 详情
(XXVI) 62445 (1S,2R)-2-phenylcyclohexyl 2-chloroacetate C14H17ClO2 详情 详情
(XXVII) 62446 (1R,2S)-2-phenylcyclohexyl (2R,3S)-3-(4-methoxyphenyl)-2-oxiranecarboxylate C22H24O4 详情 详情
(XXVIII) 62447 (1R,2S)-2-phenylcyclohexyl (2S,3S)-3-[(2-aminophenyl)sulfanyl]-2-hydroxy-3-(4-methoxyphenyl)propanoate C28H31NO4S 详情 详情
(XXIX) 62448 (2S,3S)-3-[(2-aminophenyl)sulfanyl]-2-hydroxy-3-(4-methoxyphenyl)propanoic acid C16H17NO4S 详情 详情

合成路线3

该中间体在本合成路线中的序号:(+/-)-(XXIII)

Addition of phenylmagnesium bromide to cyclohexene oxide (XXI) in the presence of CuCl gave trans-2-phenylcyclohexanol (XXII), which was further esterified with chloroacetyl chloride to afford 2-phenylcyclohexyl chloroacetate (XXIII). Enantioselective hydrolysis of the racemic ester (XXIII) by means of Pseudomonas fluorescens lipase provided pure (1R,2S)-2-phenylcyclohexanol (XXIV), which was again esterified with chloroacetyl chloride, yielding the chiral ester (XXVI). Darzen's condensation of chloro ester (XXVI) with anisaldehyde (X) led to the chiral glycidic ester (XXVII). Epoxide ring opening in (XXVII) with 2-aminothiophenol (VII) furnished amino ester (XXVIII). Intermediate thiazepinone (VIII) was then obtained by cyclization of (XXVIII) using p-toluenesulfonic acid in refluxing xylene. Alternatively, amino ester (XXVIII) was first hydrolyzed to amino acid (XXIX), which was subsequently cyclized with p-toluenesulfonic acid as above (11). The final cyclization of amino acid (XXIX) to the intermediate thiazepinone (VIII) has also been carried out in the presence of trichloroacetic acid

1 Plaum, M.J.M.; Boesten, W.H.J.; Process for the preparation of a benzothiazepine. EP 0796853; JP 1998007667; US 5859241 .
中间体序号 中间体编号 品名 CAS号 分子式 供应商 用于合成
(+/-)-(XXII) 51208 (1R,2S)-2-phenylcyclohexanol C12H16O 详情 详情
(+/-)-(XXIII) 62445 (1S,2R)-2-phenylcyclohexyl 2-chloroacetate C14H17ClO2 详情 详情
(VII) 25182 2-aminobenzenethiol 137-07-5 C6H7NS 详情 详情
(VIII) 62436 (2S,3S)-3-hydroxy-2-(4-methoxyphenyl)-2,3-dihydro-1,5-benzothiazepin-4(5H)-one C16H15NO3S 详情 详情
(X) 27251 4-methoxybenzaldehyde; Anisicaldehyde; p-anisaldehyde 123-11-5 C8H8O2 详情 详情
(XXI) 17986 7-oxabicyclo[4.1.0]heptane; cyclohexene oxide 286-20-4 C6H10O 详情 详情
(XXIV) 10492 (1S,2R)-(+)-trans-2-Phenyl-1-cyclohexanol; (1S,2R)-2-Phenylcyclohexanol 2362-61-0 C12H16O 详情 详情
(XXV) 62445 (1S,2R)-2-phenylcyclohexyl 2-chloroacetate C14H17ClO2 详情 详情
(XXVI) 62445 (1S,2R)-2-phenylcyclohexyl 2-chloroacetate C14H17ClO2 详情 详情
(XXVII) 62446 (1R,2S)-2-phenylcyclohexyl (2R,3S)-3-(4-methoxyphenyl)-2-oxiranecarboxylate C22H24O4 详情 详情
(XXVIII) 62447 (1R,2S)-2-phenylcyclohexyl (2S,3S)-3-[(2-aminophenyl)sulfanyl]-2-hydroxy-3-(4-methoxyphenyl)propanoate C28H31NO4S 详情 详情
(XXIX) 62448 (2S,3S)-3-[(2-aminophenyl)sulfanyl]-2-hydroxy-3-(4-methoxyphenyl)propanoic acid C16H17NO4S 详情 详情
Extended Information