Water → HCID 89649428, compound

HRID 2201617Notes

Reaction equation

HRID 2201617 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([OH:8])[CH:5]=[CH:6][CH:7]=1.Br[C:10]([F:17])([F:16])[C:11]([N:13]([CH3:15])[CH3:14])=[O:12].C([O-])([O-])=O.[K+].[K+].O>CC(N(C)C)=O.C1(C)C=CC=CC=1>[F:16][C:10]([F:17])([O:8][C:4]1[CH:5]=[CH:6][CH:7]=[C:2]([F:1])[CH:3]=1)[C:11]([N:13]([CH3:15])[CH3:14])=[O:12]

Participants

7

Reactant 4

HCID 962WaterHCID 97433-FluorophenolHCID 11430Potassium CarbonateHCID 13355362HCID 13355362, compound

Product 1

HCID 89649428HCID 89649428, compoundYield 89%

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 31374DimethylacetamideSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of 3-fluoro-phenol (9.8 g, 87.4 mmol), 2-bromo-2,2-difluoro-N,N-dimethyl-acetamide (18.3 g, 89.6 mmol) and K2CO3 (13.3 g, 96.2 mmol) in 75 g of dimethylacetamide (DMAC) was heated to 100° C. for 1 h and then heated to 120° C. for 2 h. The reaction mixture was then cooled to room temperature and poured on 250 mL of H2O and 50 mL of toluene. The aqueous phase was extracted with 25 g of toluene. The combined organic layers were extracted with 5% NaOH (20 g) and H2O (2×20 g) and dried over Na2SO4. The product (18.5 g, >98% purity by quant. HPLC, 77.8 mmol, 89% yield) was obtained after removal of all volatiles under reduced pressure as a slightly yellow liquid. The material could be used in subsequent steps without further purification or purified by fractionated distillation.

Workup

  1. temperatureheated to 120° C. for 2 h
  2. temperatureThe reaction mixture was then cooled to room temperature
  3. extractionThe aqueous phase was extracted with 25 g of toluene
  4. extractionThe combined organic layers were extracted with 5% NaOH (20 g) and H2O (2×20 g)
  5. dry with materialdried over Na2SO4
  6. customThe product (18.5 g, >98% purity by quant. HPLC, 77.8 mmol, 89% yield) was obtained
  7. customafter removal of all volatiles under reduced pressure as a slightly yellow liquid
  8. customThe material could be used in subsequent steps without further purification
  9. distillationpurified by fractionated distillation

Sources & evidence

ORD record
ord-c4156696a5364bc6b1dfe4c54522c296
Source dataset
uspto-grants-2016_06
Patent number
US09365495B2

Reaction notes

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