Cl[CH:2]([F:4])[F:3].[OH:5][C:6]1[CH:7]=[CH:8][C:9]([CH3:16])=[C:10]([CH:15]=1)[C:11]([O:13][CH3:14])=[O:12].[OH-].[Na+]>[Br-].C([N+](CCCC)(CCCC)CCCC)CCC.O1CCOCC1>[F:3][CH:2]([F:4])[O:5][C:6]1[CH:7]=[CH:8][C:9]([CH3:16])=[C:10]([CH:15]=1)[C:11]([O:13][CH3:14])=[O:12]Chloro(difluoro)methane is introduced with vigorous stirring for 90 minutes into a mixture of 50 g methyl 5-hydroxy-2-methylbenzoate (see below), 1.21 g tetrabutylammonium bromide, 52 g aqueous sodium hydroxide solution (50% by weight) and 500 ml dioxane. The reaction mixture is filtered and the filtrate is adjusted to pH 1-2 with 1n aqueous hydrochloric acid. The mixture is extracted with EA three times, the combined organics are dried over MgSO4, and the solvent is removed under reduced pressure. The resulting crude product is purified by filtration over a column (silica gel and PE) yielding methyl 5-(difluoromethoxy)-2-methylbenzoate, which is used for the next step without further purification.
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