2,2,2-Trifluoro-N-methoxy-N-methylacetamide → 2,2,2-Trifluoro-1-(4-fluoro-3-methoxyphenyl)ethanone

HRID 1588870Notes

Reaction equation

HRID 1588870 reaction equation
Br[C:2]1[C:3]([F:10])=[C:4]([O:8][CH3:9])[CH:5]=[CH:6][CH:7]=1.BrC1C=CC(F)=C(OC)C=1.CON(C)[C:24](=[O:29])[C:25]([F:28])([F:27])[F:26]>O1CCCC1>[F:10][C:3]1[CH:2]=[CH:7][C:6]([C:24]([C:25]([F:28])([F:27])[F:26])=[O:29])=[CH:5][C:4]=1[O:8][CH3:9]

Participants

5

Reactant 3

HCID 27823822,2,2-Trifluoro-N-methoxy-N-methylacetamideHCID 136049094-Bromo-1-fluoro-2-methoxybenzene2×HCID 197548451-Bromo-2-fluoro-3-methoxybenzene

Product 1

HCID 197548242,2,2-Trifluoro-1-(4-fluoro-3-methoxyphenyl)ethanone

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Trifluoromethyl 4-fluoro-3-phenoxyphenyl ketone may be prepared using the following procedure. Bromination of 2-fluoroanisole yields a mixture of bromo-2-fluoroanisole isomers from which 5-bromo-2-fluoroanisole is isolated. The Grignard reagent of 5-bromo-2-fluoroanisole is then prepared and is in turn reacted with N-methoxy-N-methyl-2,2,2-trifluoroacetamide in tetrahydrofuran, yielding trifluoromethyl 4-fluoro-3-methoxyphenyl ketone. This ketone is protected by formation of the corresponding ketal, which is in turn treated with trimethylsilyl iodide, sodium hydroxide, bromobenzene, and acid, yielding trifluoromethyl (4-fluoro-3-phenoxyphenyl) ketone.

Workup

  1. customis isolated

Sources & evidence

ORD record
ord-c78358fa52f34e0a85d2df630080ac7c
Source dataset
uspto-grants-1993_06
Patent number
US05223536

Reaction notes

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