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【结 构 式】

【分子编号】63030

【品名】cis-3-Hydroxy-4-phenyl-2-azetanone; (3R*,4S*)-3-Hydroxy-4-phenyl-2-azetanone

【CA登记号】

【 分 子 式 】C9H9NO2

【 分 子 量 】163.176

【元素组成】C 66.25% H 5.56% N 8.58% O 19.61%

与该中间体有关的原料药合成路线共 2 条

合成路线1

该中间体在本合成路线中的序号:(V)

A new partial synthesis for taxol has been reported: The cyclization of N-(4-methoxyphenyl)benzylideneimine (I) with acetoxyacetyl chloride (II) by means of triethylamine in dichloromethane gives cis-3-acetoxy-1-(4-methoxyphenyl)-4-phenylazetidin-2-one (III), which is treated with ceric ammonium nitrate in acetonitrile to afford cis-3-acetoxy-4-phenylazetidin-2-one (IV). Hydrolysis of (IV) with KOH in THF-water yields cis-3-hydroxy-4-phenylazetidin-2-one (V), which is submitted to optical resolution giving the (3R,4S)-isomer (VI). The reaction of (VI) with ethyl vinyl ether (VII) by means of methanesulfonic acid in THF affords (3R,4S)-3-(1-ethoxyethoxy)-4-phenylazetidin-2-one (VIII), which is benzoylated with benzoyl chloride (IX) and butyllithium in hexane to give (X). Opening of the azetidine ring of (X) with KOH in THF-water gives (2R,3S)-3-(benzamido)-2-(1-ethoxyethoxy)propanoic acid (XI), which is cyclized with potassium tert-butoxide and methanesulfonyl chloride to (4S,5R)-5-(1-ethoxyethoxy)-2,4-diphenyl-5,6-dihydro-4H-1,3-oxazin-6-one (XII). Finally, this compound is condensed with 7-O-(triethylsilyl)baccatin III (XIV) [prepared from 10-deacetylbaccatin III (XIII) by successive reaction with triethylsilyl chloride and acetyl chloride] by means of dimethylaminopyridine (DMAP) in pyridine.

1 Holton, R.A. (University of Florida); Method for preparation of taxol using an oxazinone. US 5015744 .
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) 10455 N-(4-Methoxyphenyl)-N-[(Z)-benzylidene]amine; 4-Methoxy-N-[(Z)-benzylidene]aniline 783-08-4 C14H13NO 详情 详情
(II) 10456 Acetoxiacetil chloride; 2-chloro-2-oxoethyl acetate 13831-31-7 C4H5ClO3 详情 详情
(III) 10457 (3R,4S)-1-(4-methoxyphenyl)-2-oxo-4-phenylazetanyl acetate C18H17NO4 详情 详情
(IV) 10458 (3R,4S)-2-oxo-4-phenylazetanyl acetate C11H11NO3 详情 详情
(V) 63030 cis-3-Hydroxy-4-phenyl-2-azetanone; (3R*,4S*)-3-Hydroxy-4-phenyl-2-azetanone C9H9NO2 详情 详情
(VI) 10459 (3R,4S)-3-Hydroxy-4-phenyl-2-azetanone C9H9NO2 详情 详情
(VII) 18762 1-Ethoxyethylene; Ethyl vinyl ether;Ethoxyethene 109-92-2 C4H8O 详情 详情
(VIII) 10462 (3R,4S)-3-(1-Ethoxyethoxy)-4-phenyl-2-azetanone C13H17NO3 详情 详情
(IX) 10463 Benzoyl chloride 98-88-4 C7H5ClO 详情 详情
(X) 10464 (3R,4S)-1-Benzoyl-3-(1-ethoxyethoxy)-4-phenyl-2-azetanone C20H21NO4 详情 详情
(XI) 10465 (2R,3S)-3-(Benzoylamino)-2-(1-ethoxyethoxy)-3-phenylpropionic acid C20H23NO5 详情 详情
(XII) 10466 (4S,5R)-5-(1-Ethoxyethoxy)-2,4-diphenyl-4,5-dihydro-6H-1,3-oxazin-6-one C20H21NO4 详情 详情
(XIII) 10467 (1S,2S,3R,4S,7R,9S,10S,12R,15S)-4-(acetoxy)-1,9,12,15-tetrahydroxy-10,14,17,17-tetramethyl-11-oxo-6-oxatetracyclo[11.3.1.0(3,10).0(4,7)]heptadec-13-en-2-yl benzoate 32981-86-5 C29H36O10 详情 详情
(XIV) 10468 (1S,2S,3R,4S,7R,9R,10S,12R,15S)-4,12-bis(acetoxy)-1,15-dihydroxy-10,14,17,17-tetramethyl-11-oxo-9-[(triethylsilyl)oxy]-6-oxatetracyclo[11.3.1.0(3,10).0(4,7)]heptadec-13-en-2-yl benzoate C37H52O11Si 详情 详情

合成路线2

该中间体在本合成路线中的序号:(V)

A new synthesis of paclitaxel has been reported: The cyclization of the 4-methoxyphenylimine of benzaldehyde (I) with acetoxyacetyl chloride (II) by means of triethylamine gives cis-3-acetoxy-1-(4-methoxyphenyl)-4-phenylazetidin-2-one (III), which is treated with ceric ammonium nitrate to afford cis-3-acetoxy-4-phenylazetidin-2-one (IV). The hydrolysis of (IV) with KOH in THF/water affords the corresponding hydroxy compound (V), which is submitted to optical resolution by crystallization of the 2-methoxy-2-[2-(trifluoromethyl)phenyl]acetic esters. The (3R,4S)-regioisomer (VI) is protected with ethyl vinyl ether, giving the 1-ethoxyethyl derivative (VII), which is benzoylated with benzoyl chloride and butyllithium to afford (3R,4S)-1-benzoyl-3-(1-ethoxyethoxy)-4-phenylazetidin-2-one (VIII). The condensation of (VIII) with baccatin III (IX) by means of dimethylaminopyridine (DMAP) in pyridine yields the protected paclitaxel derivative (X), which is finally deprotected with HCl in ethanol/water.

1 Holton, R.A. (University of Florida); Method for preparation of taxol. EP 0400971; US 5336785 .
中间体序号 中间体编号 品名 CAS号 分子式 供应商 用于合成
10463 Benzoyl chloride 98-88-4 C7H5ClO 详情 详情
(I) 10455 N-(4-Methoxyphenyl)-N-[(Z)-benzylidene]amine; 4-Methoxy-N-[(Z)-benzylidene]aniline 783-08-4 C14H13NO 详情 详情
(II) 10456 Acetoxiacetil chloride; 2-chloro-2-oxoethyl acetate 13831-31-7 C4H5ClO3 详情 详情
(III) 10457 (3R,4S)-1-(4-methoxyphenyl)-2-oxo-4-phenylazetanyl acetate C18H17NO4 详情 详情
(IV) 10458 (3R,4S)-2-oxo-4-phenylazetanyl acetate C11H11NO3 详情 详情
(V) 63030 cis-3-Hydroxy-4-phenyl-2-azetanone; (3R*,4S*)-3-Hydroxy-4-phenyl-2-azetanone C9H9NO2 详情 详情
(VI) 10459 (3R,4S)-3-Hydroxy-4-phenyl-2-azetanone C9H9NO2 详情 详情
(VII) 10462 (3R,4S)-3-(1-Ethoxyethoxy)-4-phenyl-2-azetanone C13H17NO3 详情 详情
(VIII) 10464 (3R,4S)-1-Benzoyl-3-(1-ethoxyethoxy)-4-phenyl-2-azetanone C20H21NO4 详情 详情
(IX) 10473 (1S,2S,3R,4S,7R,9S,10S,12R,15S)-4,12-bis(acetoxy)-1,15-dihydroxy-10,14,17,17-tetramethyl-11-oxo-9-[(triethylsilyl)oxy]-6-oxatetracyclo[11.3.1.0(3,10).0(4,7)]heptadec-13-en-2-yl benzoate C37H52O11Si 详情 详情
(X) 10505 (1S,2S,3R,4S,7R,9S,10S,12R,15S)-4,12-bis(acetoxy)-15-[[(2R,3S)-3-(benzoylamino)-2-(1-ethoxyethoxy)-3-phenylpropanoyl]oxy]-1-hydroxy-10,14,17,17-tetramethyl-11-oxo-9-[(triethylsilyl)oxy]-6-oxatetracyclo[11.3.1.0(3,10).0(4,7)]heptadec-13-en-2-yl benzoate C57H73NO15Si 详情 详情
Extended Information