(R)-2-[(2-hydroxy-3-morpholin-4-yl-propylcarbamoyl)-methyl]-4-methyl-1H-pyrrole-3-carboxylic acid ethyl ester → (R)-2-[2-(2-hydroxy-3-morpholin-4-yl-propylamino)-ethyl]-4-methyl-1H-pyrrole-3-carboxylic acid ethyl ester

Participants

Reaction Steps

(R)-2-[(2-hydroxy-3-morpholin-4-yl-propylcarbamoyl)-methyl]-4-methyl-1H-pyrrole-3-carboxylic acid ethyl ester 5c (2.332 g, 6.6 mmol) was dissolved in 23 mL of anhydrous tetrahydrofuran under an argon atmosphere, and borane-tertrahydrofuran complex in tetrahydrofuran (23.12 mL, 1 mol/L, 23.12 mmol) was then added dropwise to the solution in an ice-water bath. Upon completion of the addition, the ice-water bath was removed. The reaction system was allowed to warm up to room temperature and refluxed at 95° C. in an oil bath for 1 hour. The reaction was completed until TLC showed the disappearance of starting materials. The solvent was evaporated under reduced pressure, and 5 mL of hydrochloric acid (2N) was then added to the residue. The mixture was stirred for 0.5 hour, and 5 mL of iced water was then added to the mixture. The mixture was adjusted to pH about 10 with 10N sodium hydroxide solution. The mixture was extracted with ethyl acetate (100 mL×2). The combined organic extracts were washed with saturated brine (50 mL), dried over anhydrous magnesium sulfate, filtered to remove the drying agent and concentrated under reduced pressure to give the title compound (R)-2-[2-(2-hydroxy-3-morpholin-4-yl-propylamino)-ethyl]-4-methyl-1H-pyrrole-3-carboxylic acid ethyl ester 5d (2.1 g, yield 93.75%) as a white solid.

Provenance & Evidence