Citric Acid → N-[2-(1-aminopropyl)-5-(trifluoromethyl)benzyl]-N-[3,5-bis(trifluoromethyl)benzyl]-2-methyl-2H-tetrazol-5-amine

Participants

Reaction Steps

To a solution of 2-{[(3,5-bis-trifluoromethyl-benzyl)-(2-methyl-2H-tetrazol-5-yl)-amino]-methyl}-4-trifluoromethyl-benzonitrile (Preparation 7) (300.0 mg, 0.590 mmoles) in toluene (1.2 mL) was added ethyl magnesium bromide (0.59 mL, 1.77 mmoles of a 3M solution in ether) dropwise at room temperature and the reaction mixture was stirred for 2.5 hours. The reaction was quenched by adding methanol (0.98 mL) dropwise with stirring until methanol and toluene were thoroughly mixed. To this mixture sodium borohydride (22.3 mg, 0.590 mmoles) was added in one portion and the reaction stirred for 1.5 hours. A 10% aqueous citric acid (1.5 mL) solution was added drop wise at room temperature until bubbling stopped. The reaction mixture was made basic to pH 10 with 1 N NaOH solution. The organic layer was dried over sodium sulfate, filtered and concentrated. The crude product was purified using cation exchange resin (Waters Oasis MCX 6CC 500 mg LP Extraction Cartridge, Waters, Milford, Mass., USA) to yield the title compound (278.4 mg, 87% yield) as yellow gum. MS (ES+) Calc: 608.5, Found: 609.1 (M+1).

Provenance & Evidence