반응 #10386

반응 방정식

4-[(S)-3-(tert-butoxycarbonylamino)pyrrolidin-1-yl]-3-chloro-2,5-difluorobenzoic acid ethyl ester

cyclopropylamine

dimethyl sulfoxide

→

title compound

수율 43.2%

4-[(S)-3-tert-Butoxycarbonylaminopyrrolidin-1-yl]-3-chloro-2-cyclopropylamino-5-fluorobenzoic acid ethyl ester

수율 43.2%

용매

ethyl acetate

반응 조건

후처리

1. 1
   세척washed with saturated NaHCO3, water, and brine
2. 2
   건조The organic layer is dried over MgSO4
3. 3
   여과filtered
4. 4
   농축the filtrate is concentrated
5. 5
   기타to afford a brown residue
6. 6
   기타The residue is then purified via flash column chromatography (1:1 ethyl acetate/hexanes)

실험 절차

A solution of 4-[(S)-3-(tert-butoxycarbonylamino)pyrrolidin-1-yl]-3-chloro-2,5-difluorobenzoic acid ethyl ester (Example 2c, 9.34 g, 23.1 mmol), cyclopropylamine (16 mL, 228 mmol), and dimethyl sulfoxide (30 mL) is heated in a sealed tube at 110° C. for 3 days. After cooling to room temperature, the reaction mixture is diluted with ethyl acetate and washed with saturated NaHCO3, water, and brine. The organic layer is dried over MgSO4, filtered, and the filtrate is concentrated to afford a brown residue. The residue is then purified via flash column chromatography (1:1 ethyl acetate/hexanes) to afford the title compound (4.41 g). MS CI: m/z 442 (MH+).

출처