4-Chloro-alpha,alpha,alpha-trifluoro-3-nitrotoluene → 2-Fluoro-1-methoxy-4-(trifluoromethyl)benzene

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Reaction Steps

The 2-amino-4-trifluoromethylphenols (XI) required for the reaction sequence just described may be prepared by conventional methods. Thus 2-amino-6-fluoro-4-trifluoromethylphenol may be prepared from 2-nitro-4-trifluoromethylchlorobenzene by reacting the latter with sodium methoxide to give 2-nitro-4-trifluoromethylanilsole, and reducing this compound to 2-amino-4-trifluoromethylanisole. The latter compound may be diazotised and converted to its fluorborate salt and heated to give 2-fluoro-4-trifluoromethylanisole. This may then be nitrated to form 2-fluoro-6-nitro-4-trifluoromethyl anisole, which is then reduced to give 2-amino-6-fluoro-4-trifluoromethylanisole. Finally the latter compound is heated with a dimethylating agent, for example an excess of pyridine hydrochloride to give 2-amino-6-fluoro-4-trifluoromethylphenol.

Provenance & Evidence