Cesium carbonate → Methyl 4-(fluoromethoxy)-3-(trifluoromethyl)benzoate

HRID 1964127Notes

Reaction equation

HRID 1964127 reaction equation
[OH:1][C:2]1[CH:11]=[CH:10][C:5]([C:6]([O:8][CH3:9])=[O:7])=[CH:4][C:3]=1[C:12]([F:15])([F:14])[F:13].C(=O)([O-])[O-].[Cs+].[Cs+].Cl[CH2:23][F:24]>CN(C=O)C>[F:24][CH2:23][O:1][C:2]1[CH:11]=[CH:10][C:5]([C:6]([O:8][CH3:9])=[O:7])=[CH:4][C:3]=1[C:12]([F:13])([F:14])[F:15]

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 11643ChlorofluoromethaneHCID 13962148Methyl 4-hydroxy-3-(trifluoromethyl)benzoate

Product 1

HCID 67249754Methyl 4-(fluoromethoxy)-3-(trifluoromethyl)benzoateYield 86.9%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a cooled (−78° C.) mixture of methyl 4-hydroxy-3-(trifluoromethyl)benzoate (2.45 g, 11.13 mmol) and cesium carbonate (5.44 g, 16.7 mmol) in DMF in a pressure vessel was bubbled chlorofluoromethane (7.00 g, 102 mmol). The vessel was sealed and the reaction was stirred at room temperature for 120 h. The reaction was filtered through Celite®. The filtrate was diluted with EtOAc, washed with water (4 times), dried over MgSO4, filtered and concentrated under vacuum to give the title compound as a solid (2.44 g). LCMS m/z=253.4 [M+H]+; 1H NMR (400 MHz, DMSO-d6) δ ppm 3.88 (s, 3H), 5.98-6.20 (d, J=52.5 Hz, 2H), 7.59 (d, J=8.84 Hz, 1H), 8.18 (d, J=2.02 Hz, 1H), 8.28 (dd, J=8.84, 2.15 Hz, 1H); 19F NMR (376 MHz, DMSO-d6) δ ppm −153.52 (s, 1F), −61.08 (s, 3F).

Workup

  1. temperatureTo a cooled
  2. customThe vessel was sealed
  3. filtrationThe reaction was filtered through Celite®
  4. additionThe filtrate was diluted with EtOAc
  5. washwashed with water (4 times)
  6. dry with materialdried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated under vacuum

Sources & evidence

ORD record
ord-3dcb0e52b5164895a547fa17bdf7bc19
Source dataset
uspto-grants-2013_04
Patent number
US08415484B2

Reaction notes

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