Trifluoroacetic acid → Rac-(5-methanesulfonyl-2-morpholin-4-yl-phenyl)-[2-methyl-4-(4-trifluoromethyl-phenyl)-piperazin-1-yl]-methanone

HRID 32739Notes

Reaction equation

HRID 32739 reaction equation
C(O[C:6]([N:8]1[CH2:13][CH2:12][N:11]([C:14](=[O:31])[C:15]2[CH:20]=[C:19]([S:21]([CH3:24])(=[O:23])=[O:22])[CH:18]=[CH:17][C:16]=2[N:25]2[CH2:30][CH2:29][O:28][CH2:27][CH2:26]2)[CH:10]([CH3:32])[CH2:9]1)=O)(C)(C)C.FC(F)(F)C(O)=O.BrC1[CH:46]=[CH:45][C:44]([C:47]([F:50])([F:49])[F:48])=[CH:43][CH:42]=1>ClCCl.C1(P(C2CCCCC2)C2C=CC=CC=2C2C=CC=CC=2)CCCCC1>[CH3:24][S:21]([C:19]1[CH:18]=[CH:17][C:16]([N:25]2[CH2:26][CH2:27][O:28][CH2:29][CH2:30]2)=[C:15]([C:14]([N:11]2[CH2:12][CH2:13][N:8]([C:6]3[CH:46]=[CH:45][C:44]([C:47]([F:50])([F:49])[F:48])=[CH:43][CH:42]=3)[CH2:9][CH:10]2[CH3:32])=[O:31])[CH:20]=1)(=[O:23])=[O:22]

Participants

6

Reactant 3

HCID 6422Trifluoroacetic acidHCID 67872Benzene, 1-bromo-4-(trifluoromethyl)-HCID 59793661rac4-(5-Methanesulfonyl-2-morpholin4-yl-benzoyl)-3-methyl-piperazine-1-carboxylic acid tert-butyl ester

Product 1

HCID 68843509Rac-(5-methanesulfonyl-2-morpholin-4-yl-phenyl)-[2-methyl-4-(4-trifluoromethyl-phenyl)-piperazin-1-yl]-methanoneYield 30%

Reagents, catalysts & solvents 2

HCID 27342162-(Dicyclohexylphosphino)biphenylCatalystHCID 6344DichloromethaneSolvent

Procedure

To a solution of rac-4-(5-Methanesulfonyl-2-morpholin-4-yl-benzoyl)-3-methyl-piperazine-1-carboxylic acid tert-butyl ester (250 mg, 0.54 mmol) in dichloromethane (2 ml) was added trifluoroacetic acid (1 ml) and the reaction mixture was stirred at room temperature for 30 min. After such time the reaction mixture was concentrated in vacuo, and the residue was dissolved in toluene (5 ml). To the solution were added 1-Bromo-4-trifluoromethyl-benzene (0.15 ml, 1.1 mmol), sodium-tert butylate (128 mg, 1.4 mmol), 2-(dicyclohexylphosphino)biphenyl (3.8.mg, 0.011 mmol), and tris(dibenzylidene-acetone)dipalladium-chloroform complex (5.5 mg, 0.005 mmol). The reaction mixture was then stirred for 16 hours at 80° C. After allowing to cool to room temperature the reaction mixture was concentrated in vacuo and purified by column chromatography (SiO2, 70 g, dichloromethane/methanol 0-5%) to give the title compound (83 mg, 30%). MS (m/e): 512.3 (M+H+)

Workup

  1. concentrationAfter such time the reaction mixture was concentrated in vacuo
  2. dissolutionthe residue was dissolved in toluene (5 ml)
  3. stirringThe reaction mixture was then stirred for 16 hours at 80° C
  4. temperatureto cool to room temperature the reaction mixture
  5. concentrationwas concentrated in vacuo
  6. custompurified by column chromatography (SiO2, 70 g, dichloromethane/methanol 0-5%)

Sources & evidence

ORD record
ord-97eaaa411c6744e4a3c4ad696b2dde35
Source dataset
uspto-grants-2008_09
Patent number
US07427612B2

Reaction notes

Loading…