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

HRID 423835Notes

Reaction equation

HRID 423835 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-80e4a8f9578e4a71aab1816d1479363e
Source dataset
uspto-grants-2012_01
Patent number
US08101767B2

Reaction notes

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