Реакция #10386

Уравнение реакции

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

cyclopropylamine

dimethyl sulfoxide

→

title compound

Выход 43.2%

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

Выход 43.2%

Растворители

ethyl acetate

Условия реакции

Обработка

1. 1
   Промывкаwashed with saturated NaHCO3, water, and brine
2. 2
   СушкаThe organic layer is dried over MgSO4
3. 3
   Фильтрацияfiltered
4. 4
   Концентрированиеthe filtrate is concentrated
5. 5
   Другоеto afford a brown residue
6. 6
   ДругоеThe residue is then purified via flash column chromatography (1:1 ethyl acetate/hexanes)

Методика

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+).

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