Reaktion #10386

Reaktionsgleichung

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

cyclopropylamine

dimethyl sulfoxide

→

title compound

Ausbeute 43.2%

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

Ausbeute 43.2%

Lösungsmittel

ethyl acetate

Reaktionsbedingungen

Aufarbeitung

1. 1
   Waschenwashed with saturated NaHCO3, water, and brine
2. 2
   TrocknenThe organic layer is dried over MgSO4
3. 3
   Filtrationfiltered
4. 4
   Einengenthe filtrate is concentrated
5. 5
   Sonstigeto afford a brown residue
6. 6
   SonstigeThe residue is then purified via flash column chromatography (1:1 ethyl acetate/hexanes)

Vorschrift

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+).

Quelle