1-benzyl-3-(4-fluorophenyl)pyrrolidine -Drug Synthesis Database

【结构式】

【分子编号】30992

【品名】1-benzyl-3-(4-fluorophenyl)pyrrolidine

【CA登记号】

【分子式】C₁₇H₁₈FN

【分子量】255.3350632

【元素组成】C 79.97% H 7.11% F 7.44% N 5.49%

与该中间体有关的原料药合成路线共 2 条

合成路线1 合成路线2

合成路线1

该中间体在本合成路线中的序号：(V)

The sulfonylation of 1-benzylpyrrolidin-3-ol by means of mesyl or tosyl chlorides gives the corresponding sulfonates (II) or (III), which are condensed with the bis(4-fluorophenyl)cuprate lithium (IV) yielding 1-benzyl-3-(4-fluorophenyl) pyrrolidine (V). The debenzylation of (V) with ammonium formate over Pd/C in methanol affords 3-(4-fluorophenyl)pyrrolidine (VI), which is finally condensed with 2-(4-bromobutyl)-1,2-benzoisothiazol-3-one S,S-dioxide (VII) by means of triethylamine in acetonitrile.

参考文献中间体

合成目标

【1】 Lee, C.-H.; Ahn, K.H.; Lee, S.J.; Park, T.K.; Hong, C.Y.; N-Substituted-3-arylpyrrolidines: Potent and selective ligands at serotonin 1A receptor. Bioorg Med Chem Lett 1999, 9, 10, 1379.

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(I)	22746	1-benzyl-3-pyrrolidinol	C₁₁H₁₅NO	详情	详情
(II)	30988	1-benzyl-3-[[methyl(dimethylene)-lambda(6)-sulfanyl]oxy]pyrrolidine	C₁₄H₂₁NOS	详情	详情
(III)	30989	1-benzyl-3-pyrrolidinyl 4-methylbenzenesulfonate	C₁₈H₂₁NO₃S	详情	详情
(V)	30992	1-benzyl-3-(4-fluorophenyl)pyrrolidine	C₁₇H₁₈FN	详情	详情
(VI)	30993	3-(4-fluorophenyl)pyrrolidine	C₁₀H₁₂FN	详情	详情
(VII)	17043	2-(4-bromobutyl)-1H-1,2-benzisothiazole-1,1,3(2H)-trione	C₁₁H₁₂BrNO₃S	详情	详情

合成路线2

该中间体在本合成路线中的序号：(IV)

Treatment of 1-benzyl-3-hydroxypyrrolidine (I) with methanesulfonyl chloride in the presence of DMAP and Et3N affords mesylate (II). Subsequent displacement of the mesylate group of (II) with the diarylcuprate reagent generated from 4-fluorophenyllithium (III) and cuprous bromide gives the 3-aryl pyrrolidine (IV). The N-benzyl group of (IV) is then removed by transfer hydrogenolysis with ammonium formate and Pd/C, yielding the secondary amine (V). This is finally alkylated with 2-(4-bromobutyl)-3-oxo-1,2-benzisothiazole 1,1-dioxide (VI) in the presence of Et3N in refluxing acetonitrile.

参考文献中间体

合成目标

【1】 Lee, C.-H.; Ahn, K.H.; Lee, S.J.; Park, T.K.; Hong, C.Y.; N-Substituted-3-arylpyrrolidines: Potent and selective ligands at serotonin 1A receptor. Bioorg Med Chem Lett 1999, 9, 10, 1379.

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(I)	22746	1-benzyl-3-pyrrolidinol	C₁₁H₁₅NO	详情	详情
(II)	62833	1-benzyl-3-pyrrolidinyl methanesulfonate	C₁₂H₁₇NO₃S	详情	详情
(III)	62834	(4-fluorophenyl)lithium	C₆H₄FLi	详情	详情
(IV)	30992	1-benzyl-3-(4-fluorophenyl)pyrrolidine	C₁₇H₁₈FN	详情	详情
(V)	30993	3-(4-fluorophenyl)pyrrolidine	C₁₀H₁₂FN	详情	详情
(VI)	17043	2-(4-bromobutyl)-1H-1,2-benzisothiazole-1,1,3(2H)-trione	C₁₁H₁₂BrNO₃S	详情	详情

Extended Information