Hydrochloric Acid → ethyl 4-[2-(N-tert-butoxycarbonyl-N-methoxycarbonylaminomethyl)cyclopropyl]-2,3,5-trifluorobenzoate

HRID 981272Notes

Reaction equation

HRID 981272 reaction equation
O[CH2:2][CH:3]1[CH2:5][CH:4]1[C:6]1[C:16]([F:17])=[CH:15][C:9]([C:10]([O:12][CH2:13][CH3:14])=[O:11])=[C:8]([F:18])[C:7]=1[F:19].[CH3:20]S(Cl)(=O)=O.Cl.[K].C[N:28]([C:32]([O:34][C:35]([CH3:38])([CH3:37])[CH3:36])=[O:33])[C:29]([O-:31])=[O:30]>C(Cl)Cl.CN(C)C=O.O.C(OCC)(=O)C.C(N(CC)CC)C>[C:35]([O:34][C:32]([N:28]([CH2:2][CH:3]1[CH2:5][CH:4]1[C:6]1[C:16]([F:17])=[CH:15][C:9]([C:10]([O:12][CH2:13][CH3:14])=[O:11])=[C:8]([F:18])[C:7]=1[F:19])[C:29]([O:31][CH3:20])=[O:30])=[O:33])([CH3:38])([CH3:37])[CH3:36]

Participants

11

Reactant 5

HCID 313Hydrochloric Acid2×HCID 31297Methanesulfonyl chlorideHCID 5462222PotassiumHCID 15136264HCID 15136264, compoundHCID 86744588HCID 86744588, compound

Product 1

HCID 15136265ethyl 4-[2-(N-tert-butoxycarbonyl-N-methoxycarbonylaminomethyl)cyclopropyl]-2,3,5-trifluorobenzoateYield 82.9%

Reagents, catalysts & solvents 5

HCID 962WaterSolvent2×HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolventHCID 8471TriethylamineSolventHCID 8857Ethyl AcetateSolvent

Procedure

In 60 ml of methylene chloride was dissolved 4.00 g of ethyl 4-(2-hydroxymethylcyclopropyl)-2,3,5trifluorobenzoate. To the resulting solution were added 1.62 g of triethylamine and 1.84 g of methanesulfonyl chloride in this order with ice-cooling. The resulting mixture was stirred at room temperature for 2 hours, and 60 ml of water was added to the reaction mixture. The resulting mixture was adjusted to pH 1 with 2N hydrochloric acid. The organic layer was separated, washed with water, a saturated aqueous sodium hydrogencarbonate solution 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 60 ml of N,N-dimethylformamide. To the resulting solution was added 3.42 g of potassium salt of tert-butyl methyliminodicarboxylate with ice-cooling. The resulting mixture was stirred at room temperature for 48 hours. The reaction mixture was added to a mixture of 100 ml of ethyl acetate and 100 ml of water. The resulting mixture was adjusted to pH 1.5 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 purified by a column chromatography (eluant: toluene/ ethyl acetate=20/1) to obtain 5.22 g (yield: 82.9%) of ethyl 4-[2-(N-tert-butoxycarbonyl-N-methoxycarbonylaminomethyl)cyclopropyl]-2,3,5-trifluorobenzoate.

Workup

  1. temperaturecooling
  2. customThe organic layer was separated
  3. washwashed with water
  4. dry with materiala saturated aqueous sodium hydrogencarbonate solution and a saturated aqueous sodium chloride solution in this order, and dried over anhydrous magnesium sulfate
  5. customThe solvent was removed by distillation under reduced pressure
  6. customThe residue obtained
  7. temperaturecooling
  8. stirringThe resulting mixture was stirred at room temperature for 48 hours
  9. customThe organic layer was separated
  10. washwashed with water
  11. dry with materiala saturated aqueous sodium chloride solution in this order, and dried over anhydrous magnesium sulfate
  12. customThe solvent was removed by distillation under reduced pressure
  13. customThe residue obtained
  14. customwas purified by a column chromatography (eluant: toluene/ ethyl acetate=20/1)

Sources & evidence

ORD record
ord-4bcc91b551184491bbf9c0ea7cc5b64e
Source dataset
uspto-grants-1991_02
Patent number
US04990508

Reaction notes

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