反应详情

Concentrated sulfuric acid (2.38 mL) was stirred in an ice bath. Sodium nitrite (199 mg) was added in one portion, and the mixture was stirred for 5 minutes and allowed to warm to room temperature over 5 minutes. It was then heated to 40° C. for 10 minutes and then cooled 0° C. A solution of 5-(trifluoromethyl)-pyrazin-2-amine (313 mg) in 3.4 mL concentrated sulfuric acid was added drop-wise over 5 minutes. The reaction was allowed to stir in the ice bath for 10 minutes, then at room temperature for 10 minutes, then at 40° C. for 20 minutes. The reaction was then pipetted into stirring ice water. The aqueous layer was extracted twice with ethyl acetate, which was then washed with water and brine and dried over MgSO4. Purification by flash column chromatography (40 g, 0-100% ethyl acetate in heptanes) gave 0.239 g of Intermediate (1 h) as a white solid. MS 163.1 (M−1, APCI-).

1. temperatureIt was then heated to 40° C. for 10 minutes
2. temperaturecooled 0° C
3. waitat room temperature for 10 minutes
4. waitat 40° C. for 20 minutes
5. extractionThe aqueous layer was extracted twice with ethyl acetate, which
6. washwas then washed with water and brine
7. dry with materialdried over MgSO4
8. customPurification by flash column chromatography (40 g, 0-100% ethyl acetate in heptanes)