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

HRID 1727570Notes

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][CH2:16][C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1)([CH3:4])([CH3:3])[CH3:2].[F-:23].[K+].[K+].[Br-].Cl[C:28]([F:34])([F:33])C(OC)=O>O.[Cu]I.CN(C=O)C>[C:1]([C:5]1[CH:10]=[C:9]([C:28]([F:34])([F:23])[F:33])[C:8]([N+:12]([O-:14])=[O:13])=[CH:7][C:6]=1[O:15][CH2:16][C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1)([CH3:4])([CH3:3])[CH3:2]

Participants

Conditions

Temperature: 125 °C

Procedure

A mixture of 1-tert-butyl-2-(benzyloxy)-5-bromo-4-nitrobenzene (913 mg, 2.5 mmol), KF (291 mg, 5 mmol), KBr (595 mg, 5 mmol), CuI (570 mg, 3 mmol), methyl chlorodifluoroacetate (1.6 mL, 15 mmol) and 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-(benzyloxy)-5-(trifluoromethyl)-4-nitrobenzene (591 mg, 67%). 1H NMR (400 MHz, CDCl3) 7.66 (s, 1H), 7.37 (m, 5H), 7.19 (s, 1H), 5.21 (s, 2H), 1.32 (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-be16cf4a6eed46a987fe8698ebc57d80
Source dataset: uspto-grants-2009_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07495103B2

Reaction notes

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