Chlorodifluoromethane → 1-Bromo-4-(difluoromethoxy)-3-methoxy-2-(methoxymethoxy)benzene

HRID 2171064Notes

Reaction equation

[Br:1][C:2]1[CH:7]=[CH:6][C:5]([OH:8])=[C:4]([O:9][CH3:10])[C:3]=1[O:11][CH2:12][O:13][CH3:14].C(=O)([O-])[O-].[K+].[K+].Cl[CH:22]([F:24])[F:23]>CN(C)C=O>[Br:1][C:2]1[CH:7]=[CH:6][C:5]([O:8][CH:22]([F:24])[F:23])=[C:4]([O:9][CH3:10])[C:3]=1[O:11][CH2:12][O:13][CH3:14]

Participants

Conditions

Temperature: -45 °C

Procedure

To a stirring solution of 4-bromo-2-methoxy-3-(methoxymethoxy)phenol (700 mg, 2.66 mmol) in N,N-dimethylformamide (15 mL) was added potassium carbonate (734 mg, 5.32 mmol) cooled to −45° C. and chlorodifluoromethane (gas) was passed for 10 min and the resultant reaction mixture was heated to 80° C. for 2 h. The reaction mixture was quenched with ice-cold water and extracted with ethyl acetate (3×). The combined ethyl acetate layers were dried over anhy. sodium sulphate and concentrated under reduced pressure. Purification of the residue by flash column chromatography (silica gel, 0-5% ethyl acetate in pet ether) afforded 1-Bromo-4-(difluoromethoxy)-3-methoxy-2-(methoxymethoxy)benzene as a liquid (250 mg, 30%).

Workup

customthe resultant reaction mixture
temperaturewas heated to 80° C. for 2 h
customThe reaction mixture was quenched with ice-cold water
extractionextracted with ethyl acetate (3×)
dry with materialThe combined ethyl acetate layers were dried over anhy
concentrationsodium sulphate and concentrated under reduced pressure
customPurification of the residue by flash column chromatography (silica gel, 0-5% ethyl acetate in pet ether)

Sources & evidence

ORD record: ord-43bec21ddde84183bc6f58eb1d6e98ce
Source dataset: uspto-grants-2015_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09051290B2

Reaction notes

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