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

HRID 1607192Notes

Reaction equation

[F:1][C:2]1[C:11]([F:12])=[C:10]([CH:13]=[O:14])[CH:9]=[CH:8][C:3]=1[NH:4][C:5](=[O:7])[CH3:6].C[Mg+].[Br-].[CH3:18]C(O)=O>C1COCC1>[F:1][C:2]1[C:11]([F:12])=[C:10]([CH:13]([OH:14])[CH3:18])[CH:9]=[CH:8][C:3]=1[NH:4][C:5](=[O:7])[CH3:6]

Participants

Conditions

Temperature: 15 °C

Procedure

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).

Workup

extractionthe product extracted into 500 mL of CH2CL2
washThis extract is washed with H2O, saturated NaHCO3 and H2O (100 mL each)

Sources & evidence

ORD record: ord-2af8e1e3607545cc818a9ed3a5d7e302
Source dataset: uspto-grants-1989_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US04863959

Reaction notes

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