Sodium hydride → [4-(1,3,3-Trimethyl-6-aza-bicyclo[3.2.1]octane-6-carbonyl)-phenylamino]-acetic acid

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Reaction Steps

To a solution of [4-(1,3,3-trimethyl-6-aza-bicyclo[3.2.1]octane-6-carbonyl)-phenyl]carbamic acid tert-butyl ester (5.0 g, 13.42 mmol) in dry DMF (75 ml) was added sodium hydride (750 mg, 33.3 mmol in 60% mineral oil) and the mixture was stirred for 30 min. Bromo-acetic acid tert-butyl ester (3.14 g, 16.11 mmol) was added and the stirring was continued for an additional 1 hr. at 50° C. The reaction was quenched by addition of water (50 ml) and extracted with diethyl ether (2×50 ml). The combined organic phases were dried (Na2SO4), filtered and evaporated in vacuo. The residue was dissolved in DCM (75 ml) and TFA (40 ml) was added. The resulting mixture was stirred for 16 hrs. at room temperature and evaporated in vacuo. To the residue was added water (75 ml) and diethyl ether (25 ml) and the precipitate was filtered off, washed with diethyl ether and dried in vacuo at 50° C. affording 3.3 g (74%) of [4-(1,3,3-trimethyl-6-aza-bicyclo[3.2.1]-octane-6-carbonyl)-phenylamino]-acetic acid an solid.

Provenance & Evidence