Acetic Acid → 2',3'-Difluoro-4'-(1-hydroxyethyl)-acetanilide

Participants

Reaction Conditions

Reaction Steps

To a stirred solution of 7.7 g of 2',3'-difluoro-4'-formylacetanilide in 190 mL of THF under an N2 atmosphere is added 29 mL of a 2.85M solution of MeMgBr at a temperature of 10°-20° C. The thick suspension is stirred 20 minutes at 20°-25° C., cooled to 15° C. and 5 mL of AcOH cautiously added. The mixture is then poured onto 500 mL of ice/H2O and the product extracted into 500 mL of CH2CL2. This extract is washed with H2O, saturated NaHCO3 and H2O (100 mL each) and stripped to give 8.1 g of yellow gummy 2',3'-difluoro-4'-(1-hydroxyethyl)-acetanilide. 8.1 g of the crude 2',3'-difluoro-4'-(1-hydroxyethyl)-acetanilide is stirred in acetone (175 mL) while 54 mL of Kilianis' reagent (Fieser and Fieser, "Reagents for Organic Synthesis", Vol. I p144) is added dropwise during 30 min. at a temperature of 20°-25° C. After stirring 30 min. longer, the reaction mixture is poured onto 200 mL of ice/H2O containing 5 g of Na2S2O5. The green suspension is extracted three times with CH2Cl2 (total volume 1 L) and the organic extract is washed with H2O, saturated NaHCO3, H2O (100 mL each) and stripped in vacuo. There is obtained 5.8 g of off-white solid which is slurried with 75 mL of Et2O to afford 5.23 g (65% yield) of 4'-acetyl-2',3'-difluoroacetanilide, m.p. 149°-152° C., (Mass spectrum shows an ion of 214).

Provenance & Evidence