Chlorodifluoromethane → Methyl 5-(difluoromethoxy)-2-methylbenzoate

HRID 1914249Notes

Reaction equation

HRID 1914249 reaction equation
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]

Participants

6

Reactant 3

HCID 6372ChlorodifluoromethaneHCID 14798Sodium HydroxideHCID 13929055Methyl 5-hydroxy-2-methylbenzoate

Product 1

HCID 53418071Methyl 5-(difluoromethoxy)-2-methylbenzoate

Reagents, catalysts & solvents 2

HCID 74236Tetrabutylammonium BromideCatalystHCID 312751,4-DioxaneSolvent

Procedure

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.

Workup

  1. filtrationThe reaction mixture is filtered
  2. extractionThe mixture is extracted with EA three times
  3. dry with materialthe combined organics are dried over MgSO4
  4. customthe solvent is removed under reduced pressure
  5. filtrationThe resulting crude product is purified by filtration over a column (silica gel and PE)

Sources & evidence

ORD record
ord-bb5f7a414fdf47d9a49fa8c5864df4b8
Source dataset
uspto-grants-2013_12
Patent number
US08609848B2

Reaction notes

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