Ketoprofen → HCID 86623052, compound

HRID 1359996Notes

Reaction equation

HRID 1359996 reaction equation
[C:1]([C:8]([NH2:13])([OH:12])[CH:9]([OH:11])[CH3:10])([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].[OH:14][C:15]([CH:17]([C:19]1[CH:32]=[CH:31][CH:30]=[C:21]([C:22]([C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)=[O:23])[CH:20]=1)[CH3:18])=[O:16].CCN=C=NCCCN(C)C.Cl.C(OCC)(=O)C>ClCCl.CN(C1C=CN=CC=1)C>[C:1]([C:8]([NH2:13])([OH:12])[CH:9]([OH:11])[CH3:10])([O:3][C:4]([CH3:5])([CH3:7])[CH3:6])=[O:2].[OH:16][C:15]([CH:17]([C:19]1[CH:32]=[CH:31][CH:30]=[C:21]([C:22]([C:24]2[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=2)=[O:23])[CH:20]=1)[CH3:18])=[O:14]

Participants

7

Reactant 4

HCID 3825KetoprofenHCID 8857Ethyl AcetateHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochloride2×HCID 86623051HCID 86623051, compound

Product 1

HCID 86623052HCID 86623052, compoundYield 128.7%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent5×

Procedure

Boc-amino-1,2-propanediol (Boc-NHCH2CH(OH)CH2OH, manufactured by Aldrich Chem. Co.) (2.05 mmol) was dissolved in dichloromethane (2 ml), and a dichloromethane solution (4 ml) of ketoprofen (4.11 mmol) (manufactured by Tokyo Kasei Kogyo) and a dichloromethane solution (1 ml) of DMAP (0.803 mmol) were added thereto in this order, followed by stirring. The reaction solution was ice-cooled, and a dichloromethane solution (5 ml) of WSCI.HCl (4.94 mmol) was added thereto, followed by stirring overnight while gradually returning to room temperature. The reaction solution was ice-cooled, and a dichloromethane solution (1 ml) of WSCI.HCl (1.24 mmol) was added thereto, followed by stirring at room temperature for 1 hour and then at 35° C. for 2 hours. Ethyl acetate was added thereto, followed by washing with 5% aqueous citric acid solution, 5% aqueous sodium hydrogen carbonate solution and saturated brine consecutively. Dehydration drying with sodium sulfate was carried out, and then the solvent was evaporated under reduced pressure. The thus obtained residue was purified by silica gel column chromatography (hexane:ethyl acetate=2:1, 0.5% triethylamine) to give the titled compound (1.175 g, yield 87%). The structure was identified by 1H-NMR (CDCl3).

Workup

  1. temperaturecooled
  2. stirringby stirring overnight
  3. customwhile gradually returning to room temperature
  4. temperaturecooled
  5. stirringby stirring at room temperature for 1 hour
  6. washby washing with 5% aqueous citric acid solution, 5% aqueous sodium hydrogen carbonate solution and saturated brine consecutively
  7. dry with materialDehydration drying with sodium sulfate
  8. customthe solvent was evaporated under reduced pressure
  9. customThe thus obtained residue was purified by silica gel column chromatography (hexane:ethyl acetate=2:1, 0.5% triethylamine)

Sources & evidence

ORD record
ord-43e44e41c7b64ae8b48265cfd5bf742e
Source dataset
uspto-grants-2011_02
Patent number
US07879817B2

Reaction notes

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