2-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenyl → N,N-Diethyl-2-(4-{2-fluoro-4-[2-oxo-2-(2-phenyl-piperidin-1-yl)-ethyl]-phenyl}-piperazin-1-yl)-2-phenyl-acetamide

HRID 1927634Notes

Reaction equation

HRID 1927634 reaction equation
Cl[C:2]1[CH:7]=[CH:6][C:5]([CH2:8][C:9]([N:11]2[CH2:16][CH2:15][CH2:14][CH2:13][CH:12]2[C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)=[O:10])=[CH:4][C:3]=1[F:23].[CH2:24]([N:26]([CH2:42][CH3:43])[C:27](=[O:41])[CH:28]([C:35]1[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1)[N:29]1[CH2:34][CH2:33][NH:32][CH2:31][CH2:30]1)[CH3:25].CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C.CC(C)([O-])C.[Na+]>C1(C)C=CC=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[CH2:42]([N:26]([CH2:24][CH3:25])[C:27](=[O:41])[CH:28]([N:29]1[CH2:34][CH2:33][N:32]([C:2]2[CH:7]=[CH:6][C:5]([CH2:8][C:9](=[O:10])[N:11]3[CH2:16][CH2:15][CH2:14][CH2:13][CH:12]3[C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=3)=[CH:4][C:3]=2[F:23])[CH2:31][CH2:30]1)[C:35]1[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1)[CH3:43]

Participants

7

Reactant 4

HCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 23676156Sodium t-butoxideHCID 66663821N,N-diethyl-2-phenyl-2-piperazin-1-yl-acetamideHCID 693044472-(4-Chloro-3-fluoro-phenyl)-1-(2-phenyl-piperidin-1-yl)-ethanone

Product 1

HCID 58870682N,N-Diethyl-2-(4-{2-fluoro-4-[2-oxo-2-(2-phenyl-piperidin-1-yl)-ethyl]-phenyl}-piperazin-1-yl)-2-phenyl-acetamideYield 16.4%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolvent

Procedure

A solution of 2-(4-chloro-3-fluoro-phenyl)-1-(2-phenyl-piperidin-1-yl)-ethanone (0.25 g, 0.75 mmol), N,N-diethyl-2-phenyl-2-piperazin-1-yl-acetamide (0.23 g, 0.82 mmol), Pd2(dba)3 (0.01 g, 0.0075 mmol), XPhos (0.01 g, 0.015 mmol), and sodium t-butoxide (0.11 g, 1.05 mmol) in toluene (2 mL) was irradiated by microwave at 120° C. for 20 min. The solution was allowed to cool, filtered through diatomaceous earth, washing with DCM (10 mL). The filtrate was concentrated and the residue was purified by SiO2 column chromatography (2 M NH3 in MeOH:DCM) to provide the title compound (0.07 g, 16%). MS: 571.7. 1H NMR (CDCl3): 7.48-7.46 (m, 2H), 7.38-7.35 (m, 4H), 7.28-7.23 (m, 2H), 7.19-7.15 (m, 4H), 6.90-6.89 (m, 2H), 3.70 (bs, 2H), 3.49-3.40 (m, 6H), 3.31-3.12 (m, 8H), 2.70-2.69 (m, 4H), 1.60-1.59 (m, 3H), 1.10-1.04 (m, 6H).

Workup

  1. temperatureto cool
  2. filtrationfiltered through diatomaceous earth
  3. washwashing with DCM (10 mL)
  4. concentrationThe filtrate was concentrated
  5. customthe residue was purified by SiO2 column chromatography (2 M NH3 in MeOH:DCM)

Sources & evidence

ORD record
ord-2b1a036168c742dbbc6a7bf38cef0c6a
Source dataset
uspto-grants-2012_05
Patent number
US08183239B2

Reaction notes

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