1-[4-(2,4-difluorobenzoyl)-1-piperidinyl]-1-ethanone -Drug Synthesis Database

【结构式】

【分子编号】23040

【品名】1-[4-(2,4-difluorobenzoyl)-1-piperidinyl]-1-ethanone

【CA登记号】

【分子式】C₁₄H₁₅F₂NO₂

【分子量】267.2754464

【元素组成】C 62.91% H 5.66% F 14.22% N 5.24% O 11.97%

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：(III)

The Friedel-Crafts condensation of 1,3-difluorobenzene (I) with 1-acetylpiperidine-4-carbonyl chloride (II) by means of AlCl3 in dichloromethane gives 1-acetyl-4-(2,4-difluorobenzoyl)piperidine (III), which is hydrotyzed with refluxing 6N HCl to yield 4-(2,4-difluorobenzoyl)piperidine (IV). The reaction of (IV) with hydroxylamine in refluxing ethanol affords the corresponding oxime (V), which is cyclized by means of KOH in boiling water giving 6-fluoro-3-(4-piperidinyl)-1,2-benzisoxazole (VI). Finally, this compound is condensed with 3-(2-chloroethyl)-2-methyl-6,7,8,9-tetrahydro-4H-pyrido[1,2-a]pyrimidin-4-one (VII) by means of K2CO3 and Kl in a variety of solvents.

参考文献中间体

合成目标

【1】 Kennis, L.E.J.; Vandenberk, J. (Janssen Pharmaceutica NV); Novel 1,2-benzisoxazol-3-yl and 1, 2-benzisothiazo. EP 0196132; ES 8705881; JP 1986221186; US 4804663 .
【2】 Diller, D.; Krochmal, B.; Dolitzky, B.-Z.; Aronhime, J. (Teva Pharmaceutical Industries Ltd.; Teva Pharmaceuticals USA, Inc.); Preparation of risperidone. WO 0212200; WO 0214286 .
【3】 Castaner, J.; Prous, J.; Risperidone. Drugs Fut 1988, 13, 12, 1052.

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)	13095	m-Difluorobenzene; 1,3-Difluorobenzene	372-18-9	C₆H₄F₂	详情	详情
(II)	13700	1-Acetyl-4-piperidinecarbonyl chloride		C₈H₁₂ClNO₂	详情	详情
(III)	23040	1-[4-(2,4-difluorobenzoyl)-1-piperidinyl]-1-ethanone		C₁₄H₁₅F₂NO₂	详情	详情
(IV)	23041	(2,4-difluorophenyl)(4-piperidinyl)methanone		C₁₂H₁₃F₂NO	详情	详情
(V)	23042	(2,4-difluorophenyl)(4-piperidinyl)methanone oxime		C₁₂H₁₄F₂N₂O	详情	详情
(VI)	17910	6-fluoro-3-(4-piperidinyl)-1,2-benzisoxazole		C₁₂H₁₃FN₂O	详情	详情
(VII)	23044	3-(2-chloroethyl)-2-methyl-6,7,8,9-tetrahydro-4H-pyrido[1,2-a]pyrimidin-4-one	63234-80-0	C₁₁H₁₅ClN₂O	详情	详情

Extended Information