Sodium Carbonate → (1S)-2,2-difluoro-1-(3'-fluoro-5'-nitrobiphenyl-4-yl)ethanol

HRID 530397Notes

Reaction equation

[F:1][C:2]1[CH:7]=[C:6]([N+:8]([O-:10])=[O:9])[CH:5]=[C:4](I)[CH:3]=1.[F:12][CH:13]([F:25])[C@H:14]([C:16]1[CH:21]=[CH:20][C:19](B(O)O)=[CH:18][CH:17]=1)[OH:15].C(=O)([O-])[O-].[Na+].[Na+]>CN(C=O)C>[F:12][CH:13]([F:25])[C@H:14]([C:16]1[CH:17]=[CH:18][C:19]([C:4]2[CH:5]=[C:6]([N+:8]([O-:10])=[O:9])[CH:7]=[C:2]([F:1])[CH:3]=2)=[CH:20][CH:21]=1)[OH:15]

Participants

Conditions

Temperature: 85 °C

Procedure

A mixture of PdCl2 (dppf)—dichloromethane adduct (40.8 mg, 0.050 mmol), 1-fluoro-3-iodo-5-nitrobenzene (267 mg, 1.00 mmol), {4-[(1S)-2,2-difluoro-1-hydroxyethyl]phenyl}boronic acid (222 mg, 1.10 mmol), sodium carbonate (1.50 mL, 3.00 mmol) and DMF (5 mL) was degassed by sparging with nitrogen and then heated to 85° C. for 3 hours. Upon cooling to room temperature, the reaction mixture was diluted with water, and aqueous NH4Cl, extracted with ethyl acetate, washed with brine, dried over sodium sulfate, filtered, and concentrated in vacuo. The residue was purified by silica gel column chromatography (ethyl acetate/hexanes) to give (1S)-2,2-difluoro-1-(3′-fluoro-5′-nitrobiphenyl-4-yl)ethanol. MS ESI calc'd. for C14H11F3NO3[M+H]+ 298, found 298.

Workup

customwas degassed
customby sparging with nitrogen
temperatureUpon cooling to room temperature
additionthe reaction mixture was diluted with water, and aqueous NH4Cl
extractionextracted with ethyl acetate
washwashed with brine
dry with materialdried over sodium sulfate
filtrationfiltered
concentrationconcentrated in vacuo
customThe residue was purified by silica gel column chromatography (ethyl acetate/hexanes)

Sources & evidence

ORD record: ord-52bb75690a4e4006bb602cf7016a4353
Source dataset: uspto-grants-2016_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09353066B2

Reaction notes

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