Hydrochloric Acid → Ethyl 2-azabicyclo[2.2.1]heptane-3-carboxylate

Participants

Reaction Steps

To a solution was 2-(4-methoxybenzoyl)-2-azabicyclo[2.2.1]heptane-3-carboxylic acid (217 mg, 0.787 mmol) in dichloromethane (3.0 ml) were added oxalyl chloride (0.14 ml, 1.65 mmol) and N,N-dimethylformamide (0.06 ml, 0.787 mmol) while being cooled with ice, and the mixture was stirred at room temperature for 30 minutes. Separately, to a suspension of hydroxylamine hydrochloride (219 mg, 3.15 mmol) in tetrahydrofuran (1.0 ml)-water (0.2 ml) was added triethylamine (0.67 ml, 4.80 mmol) at 0° C., and the mixture was stirred at 0° C. for 15 minutes. To this reaction mixture was added the acid chloride solution at 0° C., and the mixture was stirred at room temperature for 4 hours. The reaction mixture was acidified with 1N hydrochloric acid and extracted with chloroform. The organic layer was washed with saturated brine and dried over magnesium sulfate. The solvent was evaporated, and the resulting residue was purified by silica gel column chromatography (2.5%–10% methanol/chloroform), to give the entitled compound (69.4 mg, 30% through the two steps of (b) and (c)).

Provenance & Evidence