Triethylamine → Ethyl 2-(4-bromo-2,5-difluoro-3-methylbenzoyl)-3-dimethylaminoacrylate

HRID 1917423

Reaction equation

HRID 1917423 reaction equation
[F:1][C:2]1[C:10]([CH3:11])=[C:9]([Br:12])[C:8]([F:13])=[CH:7][C:3]=1[C:4]([OH:6])=O.S(Cl)(Cl)=O.[CH3:18][N:19]([CH3:27])[CH:20]=[CH:21][C:22]([O:24][CH2:25][CH3:26])=[O:23].C(N(CC)CC)C>C1(C)C=CC=CC=1.CN(C)C=O>[Br:12][C:9]1[C:8]([F:13])=[CH:7][C:3]([C:4]([C:21](=[CH:20][N:19]([CH3:27])[CH3:18])[C:22]([O:24][CH2:25][CH3:26])=[O:23])=[O:6])=[C:2]([F:1])[C:10]=1[CH3:11]

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 24386Thionyl ChlorideHCID 121015Ethyl 3-(N,N-dimethylamino)acrylateHCID 212202454-Bromo-2,5-difluoro-3-methylbenzoic acid

Product 1

HCID 86664658Ethyl 2-(4-bromo-2,5-difluoro-3-methylbenzoyl)-3-dimethylaminoacrylateYield 71.2%

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 6228DimethylformamideSolvent

Procedure

2,5-Difluoro-4-bromo-3-methylbenzoic acid (10.7 g, 42.4 mmol) was dissolved in toluene (160 mL). Thionyl chloride (5.00 mL, 63.9 mmol) and dimethylformamide (5.0 mL) were added, and the mixture was heated to reflux for two hours. The solvent was evaporated under reduced pressure, and the residue was dissolved in tetrahydrofuran (300 mL). Ethyl 3-dimethylaminoacrylate (7.30 ml, 50.9 mmol) and triethylamine (7.60 mL, 54.5 mmol) were added, and the mixture was heated to reflux for three hours. The solvent was evaporated under reduced pressure, and dichloromethane and water were added to the residue to separate the layers. Then, the organic layer was dried over anhydrous sodium sulfate, and the solvent was evaporated under reduced pressure. The residue was subjected to flash column chromatography (hexane:ethyl acetate=2:1→1:1→1:2) to give the title compound (11.35 g) as a yellow oil.

Workup

  1. temperaturethe mixture was heated
  2. temperatureto reflux for two hours
  3. customThe solvent was evaporated under reduced pressure
  4. dissolutionthe residue was dissolved in tetrahydrofuran (300 mL)
  5. temperaturethe mixture was heated
  6. temperatureto reflux for three hours
  7. customThe solvent was evaporated under reduced pressure, and dichloromethane and water
  8. additionwere added to the residue
  9. customto separate the layers
  10. dry with materialThen, the organic layer was dried over anhydrous sodium sulfate
  11. customthe solvent was evaporated under reduced pressure

Sources & evidence

ORD record
ord-bb4c6055209d45bfa7fdc50545f1e448
Source dataset
uspto-grants-2013_12
Patent number
US08618094B2

Linked notes

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