Ammonia → (5R)-1-(chloroacetyl)-5-ethynyl-L-prolinamide

Participants

Reaction Conditions

Reaction Steps

To a stirred solution of (5R)-1-(chloroacetyl)-5-ethynyl-L-proline (1.89 g, 8.76 mmol) in THF (50 mL) at ±15° C. under nitrogen was added 4-methylmorpholine (1.16 mL, 10.52 mmol), and then isobutylchloroformate (1.25 mL, 9.64 mmol) over 3 minutes. A white precipitate formed. The reaction mixture was stirred at ±15° C. under nitrogen for 30 minutes, and a solution of NH3 in dioxane (0.5 M, 88 mL, 43.8 mmol) was added. The reaction mixture was stirred at ±15° C. for 30 minutes, warmed to room temperature, and stirred at that temperature for 16 hours. The reaction mixture was diluted with 4% KHSO4 to ˜pH 4 and extracted with ethyl acetate (3×). The extracts were combined, washed with brine, dried (Na2SO4), filtered and concentrated under reduced pressure. Purification by flash column chromatography (60-75% ethyl acetate/hexane) provided the titled compound. MS (CI) m/z 215 (M+1)+.

Provenance & Evidence