Cesium carbonate → 1-Acetyl-4-[4-(4-methoxy-4-phenylpiperidin-1-yl)phenyl]piperazine

HRID 1816740Notes

Reaction equation

HRID 1816740 reaction equation
[C:1]([N:4]1[CH2:9][CH2:8][N:7]([C:10]2[CH:15]=[CH:14][C:13](OS(C(F)(F)F)(=O)=O)=[CH:12][CH:11]=2)[CH2:6][CH2:5]1)(=[O:3])[CH3:2].[CH3:24][O:25][C:26]1([C:32]2[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=2)[CH2:31][CH2:30][NH:29][CH2:28][CH2:27]1.C1(P(C2C=CC=CC=2)C2C=CC3C(=CC=CC=3)C=2C2C3C(=CC=CC=3)C=CC=2P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C(=O)([O-])[O-].[Cs+].[Cs+]>C1(C)C=CC=CC=1.ClCCl.[Pd+2].C([O-])(=O)C.C([O-])(=O)C>[C:1]([N:4]1[CH2:9][CH2:8][N:7]([C:10]2[CH:15]=[CH:14][C:13]([N:29]3[CH2:30][CH2:31][C:26]([O:25][CH3:24])([C:32]4[CH:33]=[CH:34][CH:35]=[CH:36][CH:37]=4)[CH2:27][CH2:28]3)=[CH:12][CH:11]=2)[CH2:6][CH2:5]1)(=[O:3])[CH3:2]

Participants

8

Reactant 4

HCID 10796Cesium carbonateHCID 417384HCID 417384, compoundHCID 634876Binap, (A+-)-HCID 22494772Trifluoromethanesulfonic acid 4-(4-acetylpiperazin-1-yl)phenyl ester

Product 1

HCID 224947141-Acetyl-4-[4-(4-methoxy-4-phenylpiperidin-1-yl)phenyl]piperazineYield 79.1%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 1140TolueneSolventHCID 6344DichloromethaneSolvent

Procedure

A mixture of 1-acetyl-4-(4-trifluoromethanesulfonyloxyphenyl)piperazine (3 g), 4-methoxy-4-phenylpiperidine (1.63 g), acetic acid palladium(II) salt (0.11 g), racemic-2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (0.42 g) and cesium carbonate (3.88 g) in toluene (17 ml) was stirred for 30 minutes at ambient temperature. After being stirred for a further 17 hours at 100° C., the reaction mixture was diluted with dichloromethane. The suspension was filtered through celite, and the filtrate was evaporated under reduced pressure. The residue was purified by column chromatography over silica using ethyl acetate/methyl alcohol (30:1) as the elution to give 1-acetyl-4-[4-(4-methoxy-4-phenylpiperidin-1-yl)phenyl]piperazine (2.65 g).

Workup

  1. stirringAfter being stirred for a further 17 hours at 100° C.
  2. filtrationThe suspension was filtered through celite
  3. customthe filtrate was evaporated under reduced pressure
  4. customThe residue was purified by column chromatography over silica
  5. washas the elution

Sources & evidence

ORD record
ord-6cce7c9cc5d448bc90ed36f5d8764732
Source dataset
uspto-grants-2005_04
Patent number
US06884868B1

Reaction notes

Loading…