Water → 3-[3-Chloro-4-(difluoromethoxy)phenyl]-1-cyclopentylpropan-1-one

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Reaction Conditions

Reaction Steps

A mixture of 3-(3-chloro-4-hydroxyphenyl)-1-cyclopentylpropan-1-one (15 g, 59.35 mmol, Example B(58), Step 2)), methyl 2-chloro-2,2-difluoroacetate (17.15 g, 118.7 mmol, 2 equiv) and K2CO3 (12.4 g, 124.6 mmol, 2.1 equiv) in dry DMF (150 mL) was stirred at 75-80° C. for 2 h. The mixture was poured into water and extracted with ethyl acetate. The organic layer was washed with aqueous 1 M NaOH and brine. The organic phase was dried over Na2SO4, filtered, and concentrated in vacuo. The residue was subjected to fractional distillation affording 15.3 g (72%) of material that was about 80% pure by 1H NMR (bp 70° C./2 Torr). 1H NMR (CDCl3) 1.63 (m, 9H), 2.84 (m, 5H), 6.49 (t, 1H, J=72), 7.11 (m, 2H), 7.27 (s, 1H). MS calcd for C15H17F2O2Cl, 302.744; found [M−19(−F)]: 283.7 m/z.

Provenance & Evidence