4-Methylmorpholine → Chloro-N,N-dimethylformiminium chloride

Participants

Reaction Steps

Vilsmeier reagent was prepared by treatment of DMF (0.56 ml, 7.2 mM) in dichloromethane (35 ml) under argon with oxalyl chloride (0.58 ml, 6.6 mM) at -10° for 30 minutes. The (2S,4S)-4-acetylthio-1-allyloxycarbonyl-2-carboxypyrrolidine was added to this in one portion, followed by N-methylmorpholine (0.87 ml, 7.9 mM) and stirring continued for 30 minutes at -10°. After cooling to -20°, allyl 3-allyloxy-4-aminobenzoate (1.54 g, 6.6 mM) plus N-methyl morpholine (0.87 ml, 7.9 mM) dissolved in dichloromethane (20 ml) were added dropwise. The temperature was allowed to rise to 5° and stirring continued for 2 hours. After dilution with dichloromethane, the mixture was washed with a 2M aqueous solution of hydrochloric acid, water and a saturated aqueous solution of sodium bicarbonate. It was dried over MgSO4 and the solvent evaporated. Crude material was purified by medium pressure chromatography using a gradient of diethyl ether (0 to 10%) in dichloromethane to give (2S,4S)-4-acetylthio-1-allyloxycarbonyl-2-(4-allyloxycarbonyl-2-allyloxyphenylcarbamoyl)pyrrolidine (2.7 g).

Provenance & Evidence