Potassium Carbonate → N-Boc benzylamine

Participants

Reaction Steps

The compound N-Boc 2-amino-5-(trifluoromethyl)benzoic acid (S. Takagishi, et al., Synlett 1992, 360) was transformed into its methyl ester as described in procedure (80a). A solution of this ester (125 mg, 0.39 mmol) in DMF (6 mL) was charged with K2CO3 (216 mg, 1.6 mmol) and para-chlorobenzyl bromide (160 mg, 0.78 mmol). After 1.5 h, the solution was diluted with EtOAc and was washed with brine solution followed by 1N HCl solution. The organic layer was then washed with Na2CO3 solution, water, and brine. The organic layer was dried (MgSO4), filtered, and concentrated. Flash chromatography of the resulting residue provided the desired N-Boc benzylamine (69 mg), which was dissolved in THF (0.9 mL). The solution was charged with 1N LiOH (0.3 mL) and MeOH (0.3 mL). After stirring for 18 h, the THF was removed and the solution was made acidic (pH=5) with 1N HCl. This solution was extracted with EtOAc (2×). The organic layer was washed with brine, dried (Na2SO4), filtered, and concentrated to give N-Boc 2-(para-chlorobenzyl)amino-5-(trifluoromethyl)benzoic acid.

Provenance & Evidence