2,2-Difluoro-2-(fluorosulfonyl)acetic acid → methyl 3-[(2S)-1-(difluoromethoxy)propan-2-yl]oxy-5-phenylmethoxy-benzoate

HRID 1011722Notes

Reaction equation

FS([C:5]([F:10])([F:9])C(O)=O)(=O)=O.[OH:11][CH2:12][C@@H:13]([O:15][C:16]1[CH:17]=[C:18]([CH:23]=[C:24]([O:26][CH2:27][C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=2)[CH:25]=1)[C:19]([O:21][CH3:22])=[O:20])[CH3:14]>C(#N)C.[Cu]I>[F:9][CH:5]([F:10])[O:11][CH2:12][C@@H:13]([O:15][C:16]1[CH:17]=[C:18]([CH:23]=[C:24]([O:26][CH2:27][C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=2)[CH:25]=1)[C:19]([O:21][CH3:22])=[O:20])[CH3:14]

Participants

Conditions

Temperature: 45 °C

Procedure

2-(Fluorosulphonyl)difluoroacetic acid (0.239 mL, 2.31 mmol) was added dropwise, with stirring, to a degassed mixture of methyl 3-{[(1S)-2-hydroxy-1-methylethyl]oxy}-5-[(phenylmethyl)oxy]benzoate (0.73 g, 2.31 mmol) and copper (I) iodide (88 mg, 0.46 mmol) in acetonitrile (10 mL) at 45° C. The reaction was stirred at 45° C. for 24 hours. The solvent was removed in vacuo and ethyl acetate (30 mL) added. The organics were washed with water (30 mL), brine (30 mL), dried (MgSO4), filtered and the solvent removed in vacuo to give a yellow oil which was chromatographed on silica, eluting with a gradient of 0-30% ethyl acetate in isohexane, to give the desired compound (0.11 g).

Workup

customThe solvent was removed in vacuo and ethyl acetate (30 mL)
additionadded
washThe organics were washed with water (30 mL), brine (30 mL)
dry with materialdried (MgSO4)
filtrationfiltered
customthe solvent removed in vacuo
customto give a yellow oil which
customwas chromatographed on silica
washeluting with a gradient of 0-30% ethyl acetate in isohexane

Sources & evidence

ORD record: ord-e2b57f3b921946a3b7fa9e518fa338b5
Source dataset: uspto-grants-2011_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07977328B2

Reaction notes

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