Triethylamine → (E)-N-{(R)-1-Benzyl-2-[4-(4-fluoro-benzoyl)-piperidin-1-yl]-ethyl}-3-(3-cyano-phenyl)-acrylamide

HRID 434295Notes

Reaction equation

HRID 434295 reaction equation
C([C:3]1[CH:8]=[CH:7][C:6](/[CH:9]=[CH:10]/[C:11]([OH:13])=O)=[CH:5][CH:4]=1)#N.[CH2:14]([N:16](CC)CC)C.[NH2:21][C@H:22]([CH2:39][C:40]1[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=1)[CH2:23][N:24]1[CH2:29][CH2:28][CH:27]([C:30]([C:32]2[CH:37]=[CH:36][C:35]([F:38])=[CH:34][CH:33]=2)=[O:31])[CH2:26][CH2:25]1>ClCCl>[CH2:39]([C@@H:22]([NH:21][C:11](=[O:13])/[CH:10]=[CH:9]/[C:6]1[CH:5]=[CH:4][CH:3]=[C:8]([C:14]#[N:16])[CH:7]=1)[CH2:23][N:24]1[CH2:29][CH2:28][CH:27]([C:30](=[O:31])[C:32]2[CH:33]=[CH:34][C:35]([F:38])=[CH:36][CH:37]=2)[CH2:26][CH2:25]1)[C:40]1[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 735786(2E)-3-(4-Cyanophenyl)-2-propenoic acidHCID 68809327[1-((R)-2-amino-3-phenyl-propyl)-piperidin-4-yl]-(4-fluoro-phenyl)-methanone

Product 1

HCID 68811168(E)-N-{(R)-1-Benzyl-2-[4-(4-fluoro-benzoyl)-piperidin-1-yl]-ethyl}-3-(3-cyano-phenyl)-acrylamide

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent3×

Procedure

To a solution of (E)-3-(4-cyano-phenyl)-acrylic acid (0.042 g, 0.242 mmol) in dichloromethane (1 ml) is added triethylamine (0.046 ml, 0.331 mmol) and (benzotriazo-1-yloxy)tripyrrolidino-phosphonium hexafluorophosphate (0.126 g, 0.242 mmol). The reaction mixture is stirred at ambient temperature for 5 minutes and then a solution of [1-((R)-2-amino-3-phenyl-propyl)-piperidin-4-yl]-(4-fluoro-phenyl)-methanone (0.075, 0.220 mmol) in dichloromethane (1 ml) is added. Stirring is continued for a further 3 hours, then the reaction mixture is diluted with dichloromethane (25 ml) and washed with saturated sodium bicarbonate solution and saturated brine. The dichloromethane is dried over magnesium sulphate and the solvent evaporated. The crude product is purified by flash silica chromatography (ethyl acetate:hexane, 5:1 elution) to afford (E)-N-{(R)-1-Benzyl-2-[4-(4-fluoro-benzoyl)-piperidin-1-yl]-ethyl}-3-(3-cyano-phenyl)-acrylamide. [MH]+496.8.

Workup

  1. stirringStirring
  2. waitis continued for a further 3 hours
  3. washwashed with saturated sodium bicarbonate solution and saturated brine
  4. dry with materialThe dichloromethane is dried over magnesium sulphate
  5. customthe solvent evaporated
  6. customThe crude product is purified by flash silica chromatography (ethyl acetate:hexane, 5:1 elution)

Sources & evidence

ORD record
ord-de0dce3901a64251a9300f21e91b5f90
Source dataset
uspto-grants-2003_12
Patent number
US06670379B2

Reaction notes

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