Hydrochloric Acid → 1-Bromo-3-cyclopropylmethoxy-4-difluoromethoxy-2-iodobenzene

HRID 2097477Notes

Reaction equation

HRID 2097477 reaction equation
[Br:1][C:2]1[CH:7]=[CH:6][C:5]([OH:8])=[C:4]([O:9][CH2:10][CH:11]2[CH2:13][CH2:12]2)[C:3]=1[I:14].[OH-].[Na+].Cl[CH:18]([F:20])[F:19].Cl>[Br-].C([N+](CCCC)(CCCC)CCCC)CCC.C1(C)C=CC=CC=1>[Br:1][C:2]1[CH:7]=[CH:6][C:5]([O:8][CH:18]([F:20])[F:19])=[C:4]([O:9][CH2:10][CH:11]2[CH2:13][CH2:12]2)[C:3]=1[I:14]

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 6372ChlorodifluoromethaneHCID 14798Sodium HydroxideHCID 575717094-Bromo-2-cyclopropylmethoxy-3-iodophenol

Product 1

HCID 666028231-Bromo-3-cyclopropylmethoxy-4-difluoromethoxy-2-iodobenzeneYield 92.1%

Reagents, catalysts & solvents 2

HCID 74236Tetrabutylammonium BromideCatalystHCID 1140TolueneSolvent

Procedure

To 20 ml of toluene solution containing 1.84 g (5.0 mmol) of 4-bromo-2-cyclopropylmethoxy-3-iodophenol obtained in Reference example 12-(d) were added 0.8 g (2.5 mmol) of tetrabutylammonium bromide and 10 ml of 35% aqueous solution of sodium hydroxide, and then, 5.0 g (62 mmol) of chlorodifluoromethane was blown thereinto at 80° C. over 30 minutes. After completion of the reaction, 2N hydrochloric acid was added to the reaction mixture to adjust a pH thereof to 5. The organic layer after separation was washed with a saturated aqueous solution of sodium chloride, dried over anhydrous sodium sulfate and then concentrated under reduced pressure. The obtained residue was applied to silica gel column chromatography (Eluent; hexane:ethyl acetate=9:1 (V/V)), and the fractions containing the desired compound were concentrated under reduced pressure to obtain 1.93 g of the title compound as a colorless oil. (Yield: 92%)

Workup

  1. additionwas added to the reaction mixture
  2. customThe organic layer after separation
  3. washwas washed with a saturated aqueous solution of sodium chloride
  4. dry with materialdried over anhydrous sodium sulfate
  5. concentrationconcentrated under reduced pressure
  6. additionthe fractions containing the desired compound
  7. concentrationwere concentrated under reduced pressure

Sources & evidence

ORD record
ord-6301fb8ea07044d18c6d3144ca58b20b
Source dataset
uspto-grants-2013_05
Patent number
US08450319B2

Reaction notes

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