Chlorodifluoromethane → 1-bromo-3-cyclopropylmethoxy-4-difluoromethoxybenzene

HRID 2416158Notes

Reaction equation

HRID 2416158 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)[CH:3]=1.Cl[CH:15]([F:17])[F:16]>[N+](CCCC)(CCCC)(CCCC)CCCC.[Br-].O1CCOCC1>[Br:1][C:2]1[CH:7]=[CH:6][C:5]([O:8][CH:15]([F:17])[F:16])=[C:4]([O:9][CH2:10][CH:11]2[CH2:12][CH2:13]2)[CH:3]=1

Participants

5

Reactant 2

HCID 6372Chlorodifluoromethane2×HCID 10243477HCID 10243477, compound

Product 1

HCID 100172571-bromo-3-cyclopropylmethoxy-4-difluoromethoxybenzene

Reagents, catalysts & solvents 2

HCID 74236Tetrabutylammonium BromideCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
65 °C

Procedure

A mixture of crude 4-bromo-2-cyclopropylmethoxyphenol (388 g) and (n-Bu)4NBr (20 g) in dioxane (2.0 L) was heated to 65° C. Aqueous caustic solution (40%, 294 g) was added and the temperature was raised to 80° C. Chlorodifluoromethane was added below the surface via a 12 gauge needle and CF2HCl was rapidly absorbed. After about 70 minutes, the absorption of gas ceased and reaction temperature dropped to 77° C. About 184 g of chlorodifluoromethane (Fw=86.47, 2.128 mol) had been added. GC analysis of an aliquot indicated the disappearance of the starting material. The mixture was cooled to room temperature and was quenched with water (1.2 L) under CF2HCl atmosphere. Extraction with hexanes (2×750 mL) and the combined hexanes extracts were washed with water (1 L). The aqueous layer was back-extracted with hexanes (500 mL) and the combined organic extracts were dried (MgSO4) and filtered. Evaporation of the solvent under reduced pressure gave a brown oil (about 457 g). GC analysis showed 75 area % purity. The crude yield was 98% or 86% adjusted to GC area %. The crude product was distilled over a 5-plate, Older-Shaw column at 1.0 mm-Hg at 107-113° C. (overhead). Results and conditions are given in Table 3.

Workup

  1. temperaturethe temperature was raised to 80° C
  2. customwas rapidly absorbed
  3. customthe absorption of gas
  4. customreaction temperature
  5. additiondropped to 77° C
  6. temperatureThe mixture was cooled to room temperature
  7. customwas quenched with water (1.2 L) under CF2HCl atmosphere
  8. extractionExtraction with hexanes (2×750 mL)
  9. washthe combined hexanes extracts were washed with water (1 L)
  10. extractionThe aqueous layer was back-extracted with hexanes (500 mL)
  11. dry with materialthe combined organic extracts were dried (MgSO4)
  12. filtrationfiltered
  13. customEvaporation of the solvent under reduced pressure

Sources & evidence

ORD record
ord-8c34063abddb476c9f88de8406d1ec9b
Source dataset
uspto-grants-2004_11
Patent number
US06822114B1

Reaction notes

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