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

Participants

Reaction Steps

Potassium tert-butoxide (14.1 g, 125 mmol) was added to a solution of trans 4-hydroxy L-BOC-proline (9.67 g, 41.8 mmol) in DMSO (180 mL) at RT. The reaction mixture was stirred at RT for 30 min and cooled to 15° C. The product from step 3 (11.4 g, 41.8 mmol) was added to the reaction mixture as a solution in DMSO (45 mL); the reaction mixture was allowed to warm to RT and stirred for 30 min. The reaction mixture was quenched with ice-cold 10% citric acid solution and partitioned with EtOAc. The organic layer was washed with aqueous citric acid solution, water and brine, and the aqueous phases were back-extracted with EtOAc. The combined organic phases were dried over anhydrous Na2SO4, and the solvent was evaporated. LRMS ESI+ (M+H-tBu)+411.2.

Provenance & Evidence