Sodium hydride → 2-bromo-2,2-difluoro-N-(4-fluoro-2-hydroxyphenyl)acetamide
Reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([F:8])=[CH:4][C:3]=1[OH:9].[H-].[Na+].[Br:12][C:13]([F:20])([F:19])[C:14](OCC)=[O:15]>O1CCCC1>[Br:12][C:13]([F:20])([F:19])[C:14]([NH:1][C:2]1[CH:7]=[CH:6][C:5]([F:8])=[CH:4][C:3]=1[OH:9])=[O:15]Participants
5
Conditions
- Temperature
- -15 °C
Procedure
To 2-amino-5-fluorophenol (14 g, 110 mmol) in dry tetrahydrofuran at 0° C. was added sodium hydride (55 wt % in mineral oil; 4.81 g, 110 mmol). The resulting mixture was stirred for 15 minutes at −15° C. Subsequently ethyl 2-bromo-2,2-difluoroacetate (24.59 g, 121 mmol) was added dropwise and the resulting mixture was stirred at 0° C. for two hours. The reaction mixture was quenched with saturated aqueous NH4Cl solution and extracted with ethyl acetate. The combined extracts were washed with brine, dried with Na2SO4 and concentrated to yield 33 g of the title compound.
Workup
- stirringthe resulting mixture was stirred at 0° C. for two hours
- customThe reaction mixture was quenched with saturated aqueous NH4Cl solution
- extractionextracted with ethyl acetate
- washThe combined extracts were washed with brine
- dry with materialdried with Na2SO4
- concentrationconcentrated
Sources & evidence
- ORD record
- ord-b445de573cc344deb61fba6918c37468
- Source dataset
- uspto-grants-2013_07
- Patent number
- US08481723B2
Reaction notes
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