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

HRID 2189623Notes

Reaction equation

HRID 2189623 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

8

Reactant 4

HCID 73935Methyl chlorodifluoroacetateHCID 253877Potassium BromideHCID 522689Potassium FluorideHCID 574702451-Bromo-5-(tert-butyl)-4-methoxy-2-nitrobenzene

Product 1

HCID 574702461-Tert-butyl-2-methoxy-5-(trifluoromethyl)-4-nitrobenzeneYield 61.6%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 962WaterSolventHCID 6228DimethylformamideSolvent

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

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

Sources & evidence

ORD record
ord-f017baa111e1415882c3cf3cbf4993b9
Source dataset
uspto-grants-2012_12
Patent number
US08324242B2

Reaction notes

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