Hydrochloric Acid → methyl (2E)-3-{2,6-difluoro-4-[(isopropoxycarbonyl)amino]phenyl}acrylate

HRID 1179480Notes

Reaction equation

HRID 1179480 reaction equation
[H-].[Na+].[CH3:3][O:4][C:5]([CH2:7]P(OC)(OC)=O)=[O:6].[F:14][C:15]1[CH:16]=[C:17]([NH:24][C:25](=[O:30])[O:26][CH:27]([CH3:29])[CH3:28])[CH:18]=[C:19]([F:23])[C:20]=1[CH:21]=O.Cl>CN(C=O)C>[F:14][C:15]1[CH:16]=[C:17]([NH:24][C:25]([O:26][CH:27]([CH3:28])[CH3:29])=[O:30])[CH:18]=[C:19]([F:23])[C:20]=1/[CH:21]=[CH:7]/[C:5]([O:4][CH3:3])=[O:6]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 24758Sodium hydrideHCID 80029Trimethyl phosphonoacetateHCID 58978110Isopropyl 3,5-difluoro-4-formylphenylcarbamate

Product 1

HCID 58978079methyl (2E)-3-{2,6-difluoro-4-[(isopropoxycarbonyl)amino]phenyl}acrylate

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

Sodium hydride (1.4 g of 60% dispersion, 35 mmol) was placed in a flask and washed three times with hexane. The resulting solid was suspended in DMF (29 mL) and cooled to 0° C. Trimethyl phosphonoacetate (5.95 mL, 36.75 mmol) was added dropwise to this suspension to give a clear homogeneous solution. After stirring for another 15 minutes at 0° C., a solution of isopropyl 3,5-difluoro-4-formylphenylcarbamate (8.51 g, 35 mmol) in DMF (25 mL) was added dropwise. The resulting orange suspension was allowed to warm slowly to room temperature and stirred for 16 hours. The reaction mixture was then poured into 0.5 N HCl and extracted with three portions of dichloromethane. Combined organic phases were washed with saturated NaHCO3, H2O, brine, and dried (MgSO4) filtered and concentrated. The resulting orange solid was washed with hexane, 30% ethyl acetate-hexane, and then purified by column chromatography (15-30% ethyl acetate-hexane) to provide title compound.

Workup

  1. washwashed three times with hexane
  2. customto give a clear homogeneous solution
  3. temperatureto warm slowly to room temperature
  4. stirringstirred for 16 hours
  5. extractionextracted with three portions of dichloromethane
  6. washCombined organic phases were washed with saturated NaHCO3, H2O, brine
  7. dry with materialdried (MgSO4)
  8. filtrationfiltered
  9. concentrationconcentrated
  10. washThe resulting orange solid was washed with hexane, 30% ethyl acetate-hexane
  11. custompurified by column chromatography (15-30% ethyl acetate-hexane)

Sources & evidence

ORD record
ord-50fc3db8cec2469cb7f036f285997b55
Source dataset
uspto-grants-2007_10
Patent number
US07279494B2

Reaction notes

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