Triethylamine → HCID 15512824, compound

HRID 1978838Notes

Reaction equation

HRID 1978838 reaction equation
[CH2:1]([C@@H:8]([NH:25][CH3:26])[CH2:9][N:10]1[CH2:15][CH2:14][CH:13]([C:16]2[CH:21]=[C:20]([F:22])[CH:19]=[CH:18][C:17]=2[O:23][CH3:24])[CH2:12][CH2:11]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(N(CC)CC)C.[CH:34]1([N:40]=[C:41]=[O:42])[CH2:39][CH2:38][CH2:37][CH2:36][CH2:35]1>ClCCl>[CH2:1]([C@@H:8]([N:25]([CH3:26])[C:41]([NH:40][CH:34]1[CH2:39][CH2:38][CH2:37][CH2:36][CH2:35]1)=[O:42])[CH2:9][N:10]1[CH2:15][CH2:14][CH:13]([C:16]2[CH:21]=[C:20]([F:22])[CH:19]=[CH:18][C:17]=2[O:23][CH3:24])[CH2:12][CH2:11]1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 18502Cyclohexyl isocyanateHCID 15512825{(1R)-1-benzyl-2-[4-(5-fluoro-2-methoxy-phenyl)-piperidin-1-yl]-ethyl}-methyl-amine2×

Product 1

HCID 15512824HCID 15512824, compoundYield 100.7%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Under a N2 atmosphere, a solution of {(1R)-1-benzyl-2-[4-(5-fluoro-2-methoxy-phenyl)-piperidin-1-yl]-ethyl}-methyl-amine (0.12 g, 0.33 mmole, described as intermediate 7 above) and triethylamine (0.10 mL, 0.74 mmole) in dichloromethane (10 mL) was cooled to 0° C. Cyclohexyl isocyanate (0.050 rmL, 0.35 mmole) was added dropwise and the resulting mixture was stirred at 0° C. to room temperature (ice melt) overnight. The solvent was evaporated and the residue dissolved in EtOAc (25 mL) and water (25 mL). The layers were separated and the organic layer washed with water (25 mL) and brine. The combined organic washings were extracted three times with EtOAc (25 mL), then dried over Na2SO4, filtered and concentrated. Flash chromatography (elution with 7:3 EtOAc-hexane) to give 0.16 g (100% yield) of 1-{(1R)-1-benzyl-2-[4-(5-fluoro-2-methoxy-phenyl)-piperidin-1-yl]-ethyl}-3-cyclohexyl-1-methyl-urea. An ethanolic solution of the product was heated to gentle reflux and 1 equivalent of fumaric acid in hot ethyl alcohol solution was added to afford the fumarate salt of the titled compound as a white solid.

Workup

  1. customThe solvent was evaporated
  2. dissolutionthe residue dissolved in EtOAc (25 mL)
  3. customThe layers were separated
  4. washthe organic layer washed with water (25 mL) and brine
  5. extractionThe combined organic washings were extracted three times with EtOAc (25 mL)
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. washFlash chromatography (elution with 7:3 EtOAc-hexane)

Sources & evidence

ORD record
ord-c55e76258ae94bc1a5d13be4c090f105
Source dataset
uspto-grants-2001_05
Patent number
US06239126B1

Reaction notes

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