3-(Trifluoromethyl)benzylamine

402-23-3

227616-77-5

2740-83-2

437761-03-0

Synthesis of (6S)-3-{[(benzyloxy)carbonyl][3-(trifluoromethyl)benzyl]amino}-4-oxo-4,6,7,8-tetrahydropyrrolo[1,2-A]pyrimidine-6-carboxylic acid from 3-(trifluoromethyl)benzyl bromide and (S)-3-(((benzyloxy)carbonyl)amino)-4-oxo-4,6,7,8-tetrahydropyrrolo[1,2-a]pyrimidine -6-carboxylic acid (12a) was performed in the following general steps: to a mixture of acid 1i (4.50 g, 13.7 mmol) in 70 mL THF at 0 °C was added 3-(trifluoromethyl)benzyl bromide (8.35 mL, 54.7 mmol), NaH (60% dispersed in oil, 1.64 g, 41.4 mmol) and TBAI (100 mg, catalytic amount). The reaction mixture was stirred at room temperature for 15 h. The reaction was then quenched by the addition of 50 mL of H2O. The volatile solvent was removed by rotary evaporation and the resulting aqueous solution was partitioned with Et2O. The organic phase was extracted with 20% saturated NaHCO3 solution (3 times). The combined organic extracts were acidified with 1N HCl and extracted with EtOAc (5 times). The combined organic extracts were washed with brine, dried (Na2SO4), and concentrated to give 6.18 g (93% yield) of 3-(trifluoromethyl)benzylamine (12a), a product that could be used in the next step without further purification.