Pivaloyl chloride → Methyl 2-hydroxy-6-pivalamidobenzoate

Participants

Reaction Steps

A solution of methyl 2-amino-6-hydroxybenzoate (prepared according to Comess et al, US2004 167128, 3.8 g) and sodium bicarbonate (2.52 g) in ethyl acetate (75 mL) and water (17.5 mL) was stirred at room temperature and pivaloyl chloride (3.51 g) was added dropwise. The resultant mixture was stirred at room temperature for 1 hour. A further amount of pivaloyl chloride (1.75 g) was added and the mixture was stirred at room temperature for 2.5 hours. A further amount of pivaloyl chloride (1 g) was added and the mixture was stirred at room temperature for 4 hours and 20 minutes. Ethyl acetate and saturated aqueous sodium bicarbonate solution were added and the layers were separated. The organic phase was washed with brine, dried (Na2SO4), filtered and the filtrate was concentrated in vacuo. The residue was purified by chromatography on silica, eluting with a mixture of ethyl acetate and cyclohexane, with a gradient of 5-25% to give methyl 2-tert-butylcarbonylamino-6-hydroxybenzoate (4.46 g) as a white solid.

Provenance & Evidence