Water → (+/-)-cis-1-[3,5-Bis (trifluoromethyl)benzoyl]-4-[4-(cyanomethyl)-1-piperazinyl]-2-(phenylmethyl)piperidine

HRID 1530918Notes

Reaction equation

HRID 1530918 reaction equation
[F:1][C:2]([F:35])([F:34])[C:3]1[CH:4]=[C:5]([CH:27]=[C:28]([C:30]([F:33])([F:32])[F:31])[CH:29]=1)[C:6]([N:8]1[CH2:13][CH2:12][CH:11]([N:14]2[CH2:19][CH2:18][NH:17][CH2:16][CH2:15]2)[CH2:10][CH:9]1[CH2:20][C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1)=[O:7].Cl[CH2:37][C:38]#[N:39].C(=O)([O-])[O-].[Na+].[Na+].O>CC(CC(C)C)=O>[F:35][C:2]([F:34])([F:1])[C:3]1[CH:4]=[C:5]([CH:27]=[C:28]([C:30]([F:33])([F:31])[F:32])[CH:29]=1)[C:6]([N:8]1[CH2:13][CH2:12][C@H:11]([N:14]2[CH2:15][CH2:16][N:17]([CH2:37][C:38]#[N:39])[CH2:18][CH2:19]2)[CH2:10][C@@H:9]1[CH2:20][C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1)=[O:7]

Participants

6

Reactant 4

HCID 962WaterHCID 7856ChloroacetonitrileHCID 10340Sodium CarbonateHCID 18630855(+/-)-1-[3,5-Bis(trifluoromethyl)benzoyl]-2-(phenylmethyl)-4-(1-piperazinyl)piperidine

Product 1

HCID 86619154(+/-)-cis-1-[3,5-Bis (trifluoromethyl)benzoyl]-4-[4-(cyanomethyl)-1-piperazinyl]-2-(phenylmethyl)piperidineYield 53.2%

Reagents, catalysts & solvents 1

HCID 7909Methyl Isobutyl KetoneSolvent

Procedure

A mixture of (±)-1-[3,5-bis(trifluoromethyl)benzoyl]-2-(phenylmethyl)-4-(1-piperazinyl)piperidine (0.0127 mol), chloroacetonitrile (0.013 mol) and sodium carbonate (0.013 mol) in methylisobutyl keton (100 ml) was stirred and refluxed. The mixture was cooled and water was added. The organic layer was separated, dried, filtered and the solvent was evaporated. The residue was purified over silica gel on a glass filter (eluent: CH2Cl2/CH3OH 100/0, 99.5/0.5 and 99/1). The pure fractions were collected and the solvent was evaporated, yielding 3.64 g (53%) of (±)-cis-1-[3,5-bis(trifluoromethyl)benzoyl]-4-[4-(cyanomethyl)-1-piperazinyl]-2-(phenylmethyl)piperidine (intermediate 6).

Workup

  1. temperaturerefluxed
  2. temperatureThe mixture was cooled
  3. customThe organic layer was separated
  4. customdried
  5. filtrationfiltered
  6. customthe solvent was evaporated
  7. customThe residue was purified over silica gel on a glass
  8. filtrationfilter (eluent: CH2Cl2/CH3OH 100/0, 99.5/0.5 and 99/1)
  9. customThe pure fractions were collected
  10. customthe solvent was evaporated

Sources & evidence

ORD record
ord-ba8132bf47d74ee38e00b4b0d554015b
Source dataset
uspto-grants-2001_03
Patent number
US06197772B1

Reaction notes

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