Hydrochloric Acid → Methyl 3-(4-{4-[1-(2-chlorophenyl)ethoxycarbonylamino]-3-isoxazolyl}benzyloxycarbonylamino)propionate

HRID 2111020Notes

Reaction equation

HRID 2111020 reaction equation
ClC1C=CC=CC=1C([N:10]([C:14]1[C:15]([C:19]2[CH:24]=[CH:23][C:22]([CH2:25]Cl)=[CH:21][CH:20]=2)=[N:16][O:17][CH:18]=1)[C:11](=[O:13])[O-:12])C.[ClH:27].[NH2:28][CH2:29][CH2:30][C:31]([O:33][CH3:34])=[O:32].[C:35](=[O:38])([O-])[O-:36].[K+].[K+].Cl>CN(C)C=O>[Cl:27][C:20]1[CH:21]=[CH:22][CH:23]=[CH:24][C:19]=1[CH:15]([O:12][C:11]([NH:10][C:14]1[C:15]([C:19]2[CH:20]=[CH:21][C:22]([CH2:25][O:36][C:35]([NH:28][CH2:29][CH2:30][C:31]([O:33][CH3:34])=[O:32])=[O:38])=[CH:23][CH:24]=2)=[N:16][O:17][CH:18]=1)=[O:13])[CH3:14]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 11430Potassium CarbonateHCID 2734767Methyl 3-aminopropanoate hydrochlorideHCID 866074191-(2-Chlorophenyl)ethyl[3-(4-chloromethylphenyl)isoxazolyl]carbamate

Product 1

HCID 68883434Methyl 3-(4-{4-[1-(2-chlorophenyl)ethoxycarbonylamino]-3-isoxazolyl}benzyloxycarbonylamino)propionateYield 21.5%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
50 °C

Procedure

1-(2-Chlorophenyl)ethyl[3-(4-chloromethylphenyl)-4-isoxazolyl]carbamate (1.0 g, 2.56 mmol) obtained in Step B-6 of Example 1 was dissolved in N,N-dimethylformamide (30 ml), methyl 3-aminopropionate hydrochloride (1.07 g, 7.67 mmol) and potassium carbonate (2.12 g, 15.3 mmol) were added, and the mixture was stirred overnight at 50° C. 1N Hydrochloric acid was added at 0° C. to weak-acidify the reaction system, and the mixture was extracted 3 times with ethyl acetate. The organic layer was washed with saturated aqueous sodium hydrogencarbonate solution and saturated aqueous sodium chloride solution, and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure, and the residue was purified by column chromatography (methanol:dichloromethane=1:20) to give the title compound (138 mg, 11%).

Workup

  1. extractionthe mixture was extracted 3 times with ethyl acetate
  2. washThe organic layer was washed with saturated aqueous sodium hydrogencarbonate solution and saturated aqueous sodium chloride solution
  3. dry with materialdried over anhydrous sodium sulfate
  4. customThe solvent was evaporated under reduced pressure
  5. customthe residue was purified by column chromatography (methanol:dichloromethane=1:20)

Sources & evidence

ORD record
ord-6ef0096e12974c979905ddd6e5c2af7c
Source dataset
uspto-grants-2009_04
Patent number
US07517996B2

Reaction notes

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