Ammonia → 4-Chloro-5-(trifluoromethyl)pyrimidin-2-amine
Reaction equation
[NH3:1].Cl[C:3]1[N:8]=[C:7]([Cl:9])[C:6]([C:10]([F:13])([F:12])[F:11])=[CH:5][N:4]=1>CO>[Cl:9][C:7]1[C:6]([C:10]([F:13])([F:12])[F:11])=[CH:5][N:4]=[C:3]([NH2:1])[N:8]=1Participants
4
Reactant 2
Product 1
Reagents, catalysts & solvents 1
Procedure
Ammonia in methanol (7N solution, 15 mL) is added dropwise to the stirred neat 2,4-dichloro-5-(trifluoromethyl)pyrimidine (H-1) (5.0 g, 23.04 mmol) under argon, and the resulting mixture is stirred at RT for 2 h. The reaction mixture is quenched with water and then extracted with ethyl acetate (200 mL×2). The combined organic layers are washed with brine, dried over Na2SO4 and filtered. The filtrate is concentrated in vacuo and the residue is purified by flash chromatography on silica gel (0-20% ethyl acetate-hexanes) to afford the product, 4-chloro-5-(trifluoromethyl)pyrimidin-2-amine (H-2) as a white solid. The regional-isomer, 2-chloro-5-(trifluoromethyl)pyrimidin-4-amine (H-3) can also be isolated as a white solid.