Methyl chlorodifluoroacetate → 1-Tert-butyl-2-methoxy-5-(trifluoromethyl)-4-nitrobenzene

HRID 74008

Reaction equation

[C:1]([C:5]1[CH:10]=[C:9](Br)[C:8]([N+:12]([O-:14])=[O:13])=[CH:7][C:6]=1[O:15][CH3:16])([CH3:4])([CH3:3])[CH3:2].[F-:17].[K+].[K+].[Br-].Cl[C:22]([F:28])([F:27])C(OC)=O>CN(C=O)C.O.[Cu]I>[C:1]([C:5]1[CH:10]=[C:9]([C:22]([F:28])([F:17])[F:27])[C:8]([N+:12]([O-:14])=[O:13])=[CH:7][C:6]=1[O:15][CH3:16])([CH3:4])([CH3:3])[CH3:2]

Participants

Conditions

Temperature: 125 °C

Procedure

A mixture of 1-tert-butyl-2-methoxy-5-bromo-4-nitrobenzene (867 mg, 3.0 mmol), KF (348 mg, 6 mmol), KBr (714 mg, 6 mmol), CuI (684 mg, 3.6 mmol), methyl chlorodifluoroacetate (2.2 mL, 21.0 mmol) in DMF (5 mL) was stirred at 125° C. in a sealed tube overnight, cooled to room temperature, diluted with water and extracted three times with EtOAc. The combined organic layers were washed with brine and dried over anhydrous MgSO4. After removal of the solvent, the residue was purified by column chromatography (0-5% EtOAc-Hexane) to yield 1-tert-butyl-2-methoxy-5-(trifluoromethyl)-4-nitrobenzene (512 mg, 61%). 1H NMR (400 MHz, CDCl3) δ 7.60 (s, 1H), 7.29 (s, 1H), 3.90 (s, 3H), 1.33 (s, 9H).

Workup

temperaturecooled to room temperature
extractionextracted three times with EtOAc
washThe combined organic layers were washed with brine
dry with materialdried over anhydrous MgSO4
customAfter removal of the solvent
customthe residue was purified by column chromatography (0-5% EtOAc-Hexane)

Sources & evidence

ORD record: ord-e77fe0383fc346d59ce7a71dd0be2d9e
Source dataset: uspto-grants-2014_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08829204B2

Linked notes

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