Styrene Oxide → (+/-)-cis-1-[3,5-Bis(trifluoromethyl)benzoyl]-4-[4-(2-hydroxy-2-phenylethyl)-1-piperazinyl]-2-(phenylmethyl)piperidine

HRID 991365Notes

Reaction equation

HRID 991365 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].[O:36]1[CH2:38][CH:37]1[C:39]1[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=1>CO>[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]([CH2:38][CH:37]([OH:36])[C:39]3[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=3)[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

4

Reactant 2

HCID 7276Styrene OxideHCID 18630855(+/-)-1-[3,5-Bis(trifluoromethyl)benzoyl]-2-(phenylmethyl)-4-(1-piperazinyl)piperidine

Product 1

HCID 15513289(+/-)-cis-1-[3,5-Bis(trifluoromethyl)benzoyl]-4-[4-(2-hydroxy-2-phenylethyl)-1-piperazinyl]-2-(phenylmethyl)piperidineYield 7.4%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A mixture of compound 15 (0.005 mol) and 1,2-epoxyethylbenzene (0.006 mol) in methanol (50 ml) was stirred at RT for 1 hour. The mixture was stirred and refluxed for 3 hours. The solvent was evaporated and the residue was purified over silica gel on a glass filter (eluent: CH2Cl2/CH3OH 100/0, 99/1 and 98/2). The pure fractions were collected and the solvent was evaporated. The residue was purified by HPLC over silica gel (eluent: CH2Cl2/CH3OH 98/2 to 95/5). Two pure fractions were collected and their solvents were evaporated. Each residue was dried, yielding 0.7 g (23%) of (±)-cis-1-[3,5-bis(trifluoromethyl)benzoyl]-4-[4-(2-hydroxy-2-phenylethyl)-1piperazinyl]-2-(phenylmethyl)piperidine (compound 60) and 0.23 g (7%) of (±)-cis-1-[3,5-bis(trifluoromethyl)benzoyl]-4-[4-(2-hydroxy-2-phenylethyl)-1piperazinyl]-2-(phenylmethyl) piperidine (compound 61).

Workup

  1. stirringThe mixture was stirred
  2. temperaturerefluxed for 3 hours
  3. customThe solvent was evaporated
  4. customthe residue was purified over silica gel on a glass
  5. filtrationfilter (eluent: CH2Cl2/CH3OH 100/0, 99/1 and 98/2)
  6. customThe pure fractions were collected
  7. customthe solvent was evaporated
  8. customThe residue was purified by HPLC over silica gel (eluent: CH2Cl2/CH3OH 98/2 to 95/5)
  9. customTwo pure fractions were collected
  10. customtheir solvents were evaporated
  11. customEach residue was dried

Sources & evidence

ORD record
ord-9a86df771b9e4dd98bd76215e49bd19c
Source dataset
uspto-grants-2002_10
Patent number
USRE037886E1

Reaction notes

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