N,N-Dimethylaniline → (2E)-3-(4-{[(benzyloxy)carbonyl]amino}-2-fluorophenyl)prop-2-enyl diazoacetate

Participants

Reaction Conditions

Reaction Steps

To a suspension of glyoxylic acid p-toluenesulfonylhydrazone (24 g, 0.10 mol, prepared as described by C. J. Blankley, F. J. Sauter and H. O. House, Organic Syntheses, Coll. Vol. V, p. 258; John Wiley, New York (1973)) in CH2Cl2 (600 mL) at 23° C. was added commercially available 1-chloro-N,N,2-trimethyl-1-propenylamine (15 mL, 0.114 mol, 1.14 equiv.) over 5 min. The reaction mixture was stirred at the same temperature for 40 min. The reaction mixture was then cooled to 0° C. and benzyl 3-fluoro-4-[(1E)-3-hydroxyprop-1-enyl]phenylcarbamate (23 g, 0.077 mol) was added in one portion followed by the addition of N,N-dimethylaniline (12 mL, 0.095 mol). After 30 minutes, triethylamine (53 mL, 0.385 mol) was added and the mixture stirred for 30 minutes at 0° C. and 15 minutes at room temperature. The reaction mixture was then concentrated to a volume of about 100 mL and 500 mL of water added. The mixture was extracted with two portions of diethyl ether and the combined organic solutions washed with saturated NaHCO3, brine, and dried (MgSO4), filtered and concentrated. Purification by column chromatography (0-25% ethyl acetate-hexane) provided the title compound as a yellow solid.

Provenance & Evidence