Hydrochloric Acid → Methyl 4-(1-benzyloxycarbonylaminocyclopropyl)-2,3,5,6-tetrafluorobenzoate

HRID 981268Notes

Reaction equation

HRID 981268 reaction equation
C([C:4]1([C:7]2[C:16]([F:17])=[C:15]([F:18])[C:10]([C:11]([O:13][CH3:14])=[O:12])=[C:9]([F:19])[C:8]=2[F:20])[CH2:6][CH2:5]1)(O)=O.C(Cl)(=O)[O:22][CH2:23][CH3:24].[N-]=[N+]=[N-].[Na+].Cl.C[N:33](C)[CH:34]=[O:35]>O1CCOCC1.C(O)C1C=CC=CC=1.O.C(OCC)(=O)C.C(N(CC)CC)C>[CH2:23]([O:22][C:34]([NH:33][C:4]1([C:7]2[C:8]([F:20])=[C:9]([F:19])[C:10]([C:11]([O:13][CH3:14])=[O:12])=[C:15]([F:18])[C:16]=2[F:17])[CH2:5][CH2:6]1)=[O:35])[C:24]1[CH:8]=[CH:7][CH:4]=[CH:5][CH:6]=1

Participants

11

Reactant 5

HCID 313Hydrochloric AcidHCID 6228DimethylformamideHCID 10928Ethyl chloroformateHCID 33557Sodium AzideHCID 15136257Methyl 4-(1-carboxycyclopropyl)-2,3,5,6-tetrafluorobenzoate

Product 1

HCID 15136259Methyl 4-(1-benzyloxycarbonylaminocyclopropyl)-2,3,5,6-tetrafluorobenzoateYield 86.9%

Reagents, catalysts & solvents 5

HCID 244Benzyl AlcoholSolventHCID 962WaterSolventHCID 8471TriethylamineSolventHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Procedure

In 90 ml of N,N-dimethylformamide was dissolved 9.0 g of methyl 4-(1-carboxycyclopropyl)-2,3,5,6-tetrafluorobenzoate. To the resulting solution were added, with ice-cooling, 4.0 g of ethyl chlorocarbonate and 3.7 g of triethylamine in this order. The resulting mixture was stirred at the same temperature for 30 minutes. Then, 2.6 g of sodium azide was added thereto with ice-cooling. The resulting mixture was stirred at the same temperature for 1 hour. To the reaction mixture were added 150 ml of ethyl acetate and 300 ml of water in this order. The resulting mixture was adjusted to pH 1 with 2N hydrochloric acid. The organic layer was separated, washed with water and a saturated aqueous sodium chloride solution in this order, and dried over anhydrous magnesium sulfate. The solvent was removed by distillation under reduced pressure. The residue obtained was dissolved in a mixture of 90 ml of dioxane and 8.1 g of benzyl alcohol. The resulting solution was refluxed for 1 hour. The reaction mixture was concentrated under reduced pressure. The residue obtained was purified by a column chromatography (eluant: toluene) to obtain 10.6 g (yield: 86.9%) of methyl 4-(1-benzyloxycarbonylaminocyclopropyl)-2,3,5,6-tetrafluorobenzoate.

Workup

  1. additionTo the resulting solution were added, with ice-
  2. temperaturecooling
  3. temperaturewith ice-cooling
  4. stirringThe resulting mixture was stirred at the same temperature for 1 hour
  5. customThe organic layer was separated
  6. washwashed with water
  7. dry with materiala saturated aqueous sodium chloride solution in this order, and dried over anhydrous magnesium sulfate
  8. customThe solvent was removed by distillation under reduced pressure
  9. customThe residue obtained
  10. temperatureThe resulting solution was refluxed for 1 hour
  11. concentrationThe reaction mixture was concentrated under reduced pressure
  12. customThe residue obtained
  13. customwas purified by a column chromatography (eluant: toluene)

Sources & evidence

ORD record
ord-c9ed52d6321e430f91821751adce7c10
Source dataset
uspto-grants-1991_02
Patent number
US04990508

Reaction notes

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