Urea → HCID 10025688, compound

HRID 346809Notes

Reaction equation

HRID 346809 reaction equation
[NH2:1][CH2:2][CH:3]1[CH2:8][CH2:7][C:6]([N:15]([CH3:17])[CH3:16])([C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)[CH2:5][CH2:4]1.C1([O:24][C:25](=O)[NH:26][CH2:27][CH2:28][CH2:29][C:30]2[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=2)C=CC=CC=1.NC(N)=O.[Cl:41][Si](C)(C)C>O1CCOCC1.CC(C)=O.CC(=O)CC.CCOCC>[ClH:41].[CH3:16][N:15]([CH3:17])[C:6]1([C:9]2[CH:10]=[CH:11][CH:12]=[CH:13][CH:14]=2)[CH2:5][CH2:4][CH:3]([CH2:2][NH:1][C:25]([NH:26][CH2:27][CH2:28][CH2:29][C:30]2[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=2)=[O:24])[CH2:8][CH2:7]1

Participants

9

Reactant 4

HCID 1176UreaHCID 6397ChlorotrimethylsilaneHCID 12986252HCID 12986252, compoundHCID 21082146(4-Aminomethyl-1-phenylcyclohexyl)dimethylamine

Product 1

HCID 10025688HCID 10025688, compoundYield 65.7%

Reagents, catalysts & solvents 4

HCID 180AcetoneSolventHCID 3283Diethyl EtherSolventHCID 6569Methyl Ethyl KetoneSolventHCID 312751,4-DioxaneSolvent

Procedure

A mixture of the diastereoisomers of (4-aminomethyl-1-phenylcyclohexyl)dimethylamine (466 mg, 2.0 mmol.) was added to a solution of (3-phenylpropyl)carbamic acid phenyl ester (511 mg, 2.0 mmol.) in dioxane (15 ml), and heating was carried out for 12 h at reflux. For working up, the mixture was concentrated, water (10 ml) was added to the residue, the pH was adjusted to 11 with 5M NaOH, and extraction was carried out with EE (3×20 ml). The combined extracts were washed with 1M NaOH (1×5 ml), dried, filtered and concentrated. The residue was a diastereoisomeric mixture of the target products, which was separated by flash chromatography on silica gel (60 g) and purified (eluant: 1000 ml of ethanol/EE 1:1). The non-polar urea (310 mg, 0.79 mmol., yellow oil) was dissolved in acetone (5 ml) and 2-butanone (15 ml), and chlorotrimethylsilane (150 μl, 1.2 mmol.) was added dropwise at RT, with stirring. After stirring for 1 h, the reaction solution was reduced to about 1 ml in vacuo, ether (10 ml) was added thereto, and vigorous stirring was carried out for 1 h at RT. The solid that formed was filtered off with suction, washed with ether (3×3 ml) and dried in vacuo. 339 mg of the hydrochloride of the non-polar diastereoisomer of 1-(4-dimethylamino-4-phenylcyclohexylmethyl)-3-(3-phenylpropyl)urea were obtained (white solid, m.p. 85–95° C.).

Workup

  1. temperatureheating
  2. temperatureat reflux
  3. concentrationthe mixture was concentrated
  4. additionwater (10 ml) was added to the residue
  5. extractionthe pH was adjusted to 11 with 5M NaOH, and extraction
  6. washThe combined extracts were washed with 1M NaOH (1×5 ml)
  7. customdried
  8. filtrationfiltered
  9. concentrationconcentrated
  10. additiona diastereoisomeric mixture of the target products, which
  11. customwas separated by flash chromatography on silica gel (60 g)
  12. custompurified (eluant: 1000 ml of ethanol/EE 1:1)
  13. stirringAfter stirring for 1 h
  14. additionwas added
  15. stirringvigorous stirring
  16. waitwas carried out for 1 h at RT
  17. customThe solid that formed
  18. filtrationwas filtered off with suction
  19. washwashed with ether (3×3 ml)
  20. customdried in vacuo

Sources & evidence

ORD record
ord-7407c9f9923247cdb643ba459d4057e4
Source dataset
uspto-grants-2007_02
Patent number
US07173045B2

Reaction notes

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