4-Methylmorpholine → HCID 117869999, compound

Participants

Reaction Conditions

Reaction Steps

To a stirred solution of 1-{(S)-2-[(S)-2-(tert-butoxycarbonyl-methyl-amino)-propionyl amino]-3-methyl-butyryl}-2,3-dihydro-1H-pyrrolo[2,3-b]pyridine-2-carboxylic acid (Intermediate 1) (3.8 g, 8.48 mmol) in THF (65 mL) were added N-methylmorpholine (1.11 mL, 10.17 mmol) followed by the addition of isobutyl chloroformate (1.32 mL, 10.17 mmol) at −20° C. The reaction mixture was stirred at −20° C. for 10 min and the white precipitate of N-methylmorpholine hydrochloride salt was removed by filtration. The filtrate was cooled to −20° C., NaBH4 (483 mg, 12.72 mmol) was added followed by cold water (30 mL) at −20° C. After 30 min the reaction mixture was poured into water (25 mL) and extracted with ethyl acetate (80 mL×2). The combined organic layers were washed with water, brine, dried over Na2SO4 and concentrated in vacuo. The resulting residue was purified by flash chromatography (silica gel, 28% EtOAc in hexanes) to give {(S)-1-[(S)-1-(2-hydroxymethyl-2,3-dihydro-pyrrolo[2,3-b]pyridine-1-carbonyl)-2-methyl-propylcarbamoyl]-ethyl}-methyl-carbamic acid tert-butyl ester (2.7 g), m/z=435 (M+H)

Provenance & Evidence