Citric Acid → HCID 178468419, compound

HRID 333437Notes

Reaction equation

HRID 333437 reaction equation
[NH2:1][C@H:2]([CH2:22][C:23]1[CH:28]=[CH:27][C:26]([Cl:29])=[CH:25][CH:24]=1)[C:3]([N:5]1[CH2:10][CH2:9][C:8]([CH:16]2[CH2:21][CH2:20][CH2:19][CH2:18][CH2:17]2)([C:11]([O:13][CH2:14][CH3:15])=[O:12])[CH2:7][CH2:6]1)=[O:4].Cl[C:31](OC1C=CC([N+]([O-])=O)=CC=1)=[O:32].[NH4+].[OH-].[NH2:45][CH2:46][CH2:47][C:48]1[N:52]=[CH:51][NH:50][CH:49]=1.C(O)(=O)CC(CC(O)=O)(C(O)=O)O>ClCCl.CN(C=O)C>[Cl:29][C:26]1[CH:27]=[CH:28][C:23]([CH2:22][C@@H:2]([NH:1][C:31]([NH:45][CH2:46][CH2:47][C:48]2[N:52]=[CH:51][NH:50][CH:49]=2)=[O:32])[C:3]([N:5]2[CH2:10][CH2:9][C:8]([CH:16]3[CH2:21][CH2:20][CH2:19][CH2:18][CH2:17]3)([C:11]([O:13][CH2:14][CH3:15])=[O:12])[CH2:7][CH2:6]2)=[O:4])=[CH:24][CH:25]=1

Participants

8

Reactant 5

HCID 311Citric AcidHCID 14923Ammonium HydroxideHCID 821294-Nitrophenyl chloroformateHCID 66987921HCID 66987921, compoundHCID 178419017HCID 178419017, compound

Product 1

HCID 178468419HCID 178468419, compoundYield 15%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

200 mg (0.48 mmol) of ethyl 1-[(R)-2-amino-3-(4-chlorophenyl)propionyl]-4-cyclohexylpiperidine-4-carboxylate and 105 mg (0.52 mmol) of para-nitrophenyl chloroformate are dissolved in 5 mL of dichloromethane. The mixture is stirred for 2 hours at room temperature and the solution is then poured into aqueous 20% NH4OH solution and extracted with dichloromethane. The organic phase is washed with water and then dried over sodium sulfate and evaporated. The colourless oil obtained is diluted in 5 mL of DMF, the mixture is heated to 80° C., 58 mg (0.52 mmol) of histamine are then added and the solution is stirred for 5 minutes at 80° C. and for 10 minutes at room temperature. The reaction is stopped by adding aqueous 5% citric acid solution, and the organic products are extracted with DCM. The organic phase is washed with aqueous 1N NaOH solution and then with water. After drying over sodium sulfate and evaporation, the crude product obtained is chromatographed on silica gel (eluent: 80/20 DCM/MeOH). 40 mg of ethyl 1-((R)-3-(4-chlorophenyl)-2-{3-[2-(1H-imidazol-4-yl)ethyl]ureido}propionyl)-4-cyclohexylpiperidine-4-carboxylate in the form of a colourless oil are obtained in a yield of 15%.

Workup

  1. extractionextracted with dichloromethane
  2. washThe organic phase is washed with water
  3. dry with materialdried over sodium sulfate
  4. customevaporated
  5. customThe colourless oil obtained
  6. temperaturethe mixture is heated to 80° C.
  7. stirringthe solution is stirred for 5 minutes at 80° C. and for 10 minutes at room temperature
  8. extractionthe organic products are extracted with DCM
  9. washThe organic phase is washed with aqueous 1N NaOH solution
  10. dry with materialAfter drying over sodium sulfate and evaporation
  11. customthe crude product obtained
  12. customis chromatographed on silica gel (eluent: 80/20 DCM/MeOH)

Sources & evidence

ORD record
ord-3f4e6c156ffc4030a4a25e75c55e76cd
Source dataset
uspto-grants-2014_11
Patent number
US08877968B2

Reaction notes

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