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

HRID 1453211Notes

Reaction equation

[Cl:1][C:2]1[CH:3]=[C:4]([CH2:9][CH2:10][C:11]([CH:13]2[CH2:17][CH2:16][CH2:15][CH2:14]2)=[O:12])[CH:5]=[CH:6][C:7]=1[OH:8].Cl[C:19]([F:25])([F:24])C(OC)=O.C([O-])([O-])=O.[K+].[K+].O>CN(C=O)C>[Cl:1][C:2]1[CH:3]=[C:4]([CH2:9][CH2:10][C:11]([CH:13]2[CH2:17][CH2:16][CH2:15][CH2:14]2)=[O:12])[CH:5]=[CH:6][C:7]=1[O:8][CH:19]([F:25])[F:24]

Participants

Conditions

Temperature: 77.5 °C

Procedure

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.

Workup

extractionextracted with ethyl acetate
washThe organic layer was washed with aqueous 1 M NaOH and brine
dry with materialThe organic phase was dried over Na2SO4
filtrationfiltered
concentrationconcentrated in vacuo
distillationThe residue was subjected to fractional distillation

Sources & evidence

ORD record: ord-79fd6068276e4e7f84aa3924647dc9fe
Source dataset: uspto-grants-2009_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07473790B2

Reaction notes

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