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

HRID 2425475Notes

Reaction equation

[F:1][C:2]([F:10])(S(F)(=O)=O)C(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:1][CH:2]([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

2,2-Difluoro-2-fluorosulfonyl-acetic acid (CAS no. 1717-59-5) (0.239 mL, 2.31 mmol) was added dropwise, with stirring, to a degassed mixture of methyl 3-[(2S)-1-hydroxypropan-2-yl]oxy-5-phenylmethoxy-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. The residue was chromatographed on silica, eluting with a gradient of 0-30% ethyl acetate in isohexane, to give the desired compound (0.11 g).

Workup

addition1717-59-5) (0.239 mL, 2.31 mmol) was added dropwise
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
customThe residue was chromatographed on silica
washeluting with a gradient of 0-30% ethyl acetate in isohexane

Sources & evidence

ORD record: ord-5e220bcbc9dc48ceafb6f6d0d4d45bef
Source dataset: uspto-grants-2011_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07964725B2

Reaction notes

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