Hydrochloric Acid → methyl (2E)-3-(4-{[(benzyloxy)carbonyl]amino}-2-fluorophenyl)acrylate

HRID 1179488Notes

Reaction equation

HRID 1179488 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:23][C:24](=[O:33])[O:25][CH2:26][C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)[CH:18]=[CH:19][C:20]=1[CH:21]=O.Cl>CN(C=O)C>[CH2:26]([O:25][C:24]([NH:23][C:17]1[CH:18]=[CH:19][C:20](/[CH:21]=[CH:7]/[C:5]([O:4][CH3:3])=[O:6])=[C:15]([F:14])[CH:16]=1)=[O:33])[C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 24758Sodium hydrideHCID 80029Trimethyl phosphonoacetateHCID 58978059Benzyl (3-fluoro-4-formylphenyl)carbamate

Product 1

HCID 58978082methyl (2E)-3-(4-{[(benzyloxy)carbonyl]amino}-2-fluorophenyl)acrylate

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

Sodium hydride (7.2 g of a 60% dispersion, 0.188 mol) was placed in a flask and washed three times with hexane. The resulting solid was suspended in DMF (140 mL) and cooled to 0° C. Trimethyl phosphonoacetate (30.7 mL, 0.190 mol) was added dropwise to this suspension to give a clear homogeneous solution. After stirring for another 20 minutes at 0° C., a solution of benzyl 3-fluoro-4-formylphenylcarbamate (2) (48 g, 0.176 mol) in DMF (140 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 poured into 0.5 N HCl (1.5 L) and extracted with three 300 mL portions of dichloromethane. Combined organic phases were washed with saturated NaHCO3, twice with H2O, brine, and dried (Na2SO4). While concentrating the solution on a rotary evaporator, the product precipitated from solution and these solids were collected on a filter (33.4 g). The filtrate was concentrated to give more solids that were washed with ether (additional 8.4 g obtained).

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 300 mL portions of dichloromethane
  6. washCombined organic phases were washed with saturated NaHCO3, twice with H2O, brine
  7. dry with materialdried (Na2SO4)
  8. concentrationWhile concentrating the solution
  9. customon a rotary evaporator
  10. customthe product precipitated from solution
  11. customthese solids were collected on
  12. filtrationa filter (33.4 g)
  13. concentrationThe filtrate was concentrated
  14. customto give more solids that
  15. washwere washed with ether (additional 8.4 g obtained)

Sources & evidence

ORD record
ord-b28018ac5c37424bb3bf03a107414a3b
Source dataset
uspto-grants-2007_10
Patent number
US07279494B2

Reaction notes

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