1-Bromo-2,4-difluorobenzene → (2S,4S)-1-Boc-4-[(2,4-difluorophenyl)amino]-2-[(4-methylpiperazin-1-yl)carbonyl]pyrrolidine

温度

110 °C

(2S,4S)-1-Boc-4-amino-2-[(4-methylpiperazin-1-yl)carbonyl]pyrrolidine (10.61 g, 33.96 mmol) obtained in Step C was dissolved in toluene (100 mL). Sodium t-butoxide (3.73 g, 38.81 mmol), 2-(di-t-butylphosphino)biphenyl (863 mg, 2.89 mmol), Tris(dibenzylideneacetone)-dipalladium(0) (1.73 g, 1.93 mmol) and 1-bromo-2,4-difluorobenzene (7.48 g, 38.81 mmol) were added thereto and the reaction solution was stirred for 10 hours at 110° C. After the reaction was completed, solid like material was filtered using the Cellite from the reaction solution. The reaction solution was diluted with EtOAc and washed with water. The extracted organic solution was dried over MgSO4, concentrated in vacuo and purified by column chromatography (eluent: MC:MeOH=10/1) to give the title compound (11.24 g, 78%).

1. filtrationsolid like material was filtered
2. additionThe reaction solution was diluted with EtOAc
3. washwashed with water
4. dry with materialThe extracted organic solution was dried over MgSO4
5. concentrationconcentrated in vacuo
6. custompurified by column chromatography (eluent: MC:MeOH=10/1)

ORDレコード

ord-e56434fa315b47b5b5134825a7861fa7

出典データセット

uspto-grants-2012_05

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US08183243B2