(2S,4R)-4-hydroxy-1-[(2-methylpropan-2-yl)oxycarbonyl]pyrrolidine-2-carboxylic acid → Ethyl (4R)-4-[(7-bromo-6-methoxyisoquinolin-1-yl)oxy]-L-prolinate hydrochloride

Participants

Reaction Conditions

Reaction Steps

Potassium t-butoxide (618 mg, 5.5 mmol) was added to a stirred solution of BOC trans-4-hydroxyproline (424 mg, 1.83 mmol) in DMSO (10 mL) at RT. The reaction mixture was stirred for 30 minutes, cooled to 15° C. and the product from Step 3 (500 mg, 1.83 mmol) added. The reaction mixture was stirred overnight and partitioned between ice-cold 10% citric acid and EtOAc. The organic phase was washed with water and brine, dried over Na2SO4 and the solvent evaporated. The crude product was dissolved in EtOH (100 mL), cooled to 0° C., and HCl was bubbled through until saturated. The reaction mixture was allowed to warm to RT and stirred for 24 hours. The volatiles were evaporated and the residue azeotroped with EtOH (×4) to give the title compound as a tan solid (555 mg). LRMS ESI− (M+H)+395.0.

Provenance & Evidence