tert-Butyl 2-(4-bromophenyl)pyrrolidine-1-carboxylate → tert-butyl 2-(4'-((1R,2S)-2-(2,2-dichloroacetamido)-3-fluoro-1-hydroxypropyl)-[1,1'-biphenyl]-4-yl)pyrrolidine-1-carboxylate

関与物質

役割	名称	HCID	仕込み量
反応物	tert-Butyl 2-(4-bromophenyl)pyrrolidine-1-carboxylate	HCID 53407516	—
反応物	2,2-Dichloro-N-[(1S,2R)-1-fluoromethyl-2-hydroxy-2-(4-trimethylstannanyl-phenyl)-ethyl]-acetamide	HCID 86695383	—
触媒	Bis(dibenzylideneacetone)palladium	HCID 9811564	—
溶媒	Dimethylformamide	HCID 6228	—
生成物	tert-butyl 2-(4'-((1R,2S)-2-(2,2-dichloroacetamido)-3-fluoro-1-hydroxypropyl)-[1,1'-biphenyl]-4-yl)pyrrolidine-1-carboxylate	HCID 89519230	29.9%

反応条件

温度	80 °C

反応手順

A mixture of commercially available 2-(4-Bromo-phenyl)-pyrrolidine-1-carboxylic acid tert-butyl ester (500 mg, 1.53 mmol), 2,2-dichloro-N-((1R,2S)-3-fluoro-1-hydroxy-1-(4-(trimethylstannyl)phenyl)propan-2-yl)acetamide (679 mg, 1.53 mmol, 1 eq.), P(2-fur)3 (72 mg, 0.31 mmol, 0.2 eq.) and Pd2(dba)3 (142 mg, 0.153 mmol, 0.1 eq.) are dissolved in DMF (8 mL, 0.2 M) and de-oxygenated. The mixture is heated to 80° C. for 16 hours. Reaction is concentrated under vacuum to a syrup and purified on a 24 g silica column eluting from 0-100% EtOAc/heptane) to give the title compound 240 mg.

情報源と証拠

DOI	10.6084/m9.figshare.5104873.v1
特許番号	US09145355B2
出典データセット	uspto-grants-2015_09
ORD ID	ord-2d789eb8fb494af0ae133c8b92b68538
出典メモ	uspto-grants-2015_09