Dimethyl Sulfoxide → (2R)-1-[3,5-bis(trifluoromethyl)benzoyl]-2-(3,4-dimethylbenzyl)-4-[2-(formylmethoxy)ethyl]piperazine

HRID 584185Notes

Reaction equation

HRID 584185 reaction equation
C(Cl)(=O)C(Cl)=O.CS(C)=O.[F:11][C:12]([F:47])([F:46])[C:13]1[CH:14]=[C:15]([CH:39]=[C:40]([C:42]([F:45])([F:44])[F:43])[CH:41]=1)[C:16]([N:18]1[CH2:23][CH2:22][N:21]([CH2:24][CH2:25][O:26][CH2:27][CH2:28][OH:29])[CH2:20][C@H:19]1[CH2:30][C:31]1[CH:36]=[CH:35][C:34]([CH3:37])=[C:33]([CH3:38])[CH:32]=1)=[O:17].[Cl-].[NH4+]>ClCCl.C(N(CC)CC)C>[F:47][C:12]([F:11])([F:46])[C:13]1[CH:14]=[C:15]([CH:39]=[C:40]([C:42]([F:43])([F:44])[F:45])[CH:41]=1)[C:16]([N:18]1[CH2:23][CH2:22][N:21]([CH2:24][CH2:25][O:26][CH2:27][CH:28]=[O:29])[CH2:20][C@H:19]1[CH2:30][C:31]1[CH:36]=[CH:35][C:34]([CH3:37])=[C:33]([CH3:38])[CH:32]=1)=[O:17]

Participants

7

Reactant 4

HCID 679Dimethyl SulfoxideHCID 25517Ammonium ChlorideHCID 65578Oxalyl chlorideHCID 86588510(2R)-1-[3,5-bis(trifluoromethyl)benzoyl]-2-(3,4-dimethylbenzyl)-4-[2-(2-hydroxyethoxy)ethyl]piperazine

Product 1

HCID 86588511(2R)-1-[3,5-bis(trifluoromethyl)benzoyl]-2-(3,4-dimethylbenzyl)-4-[2-(formylmethoxy)ethyl]piperazineYield 54.1%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolvent2×HCID 8471TriethylamineSolvent

Conditions

Temperature
-45 °C

Procedure

To a stirred solution of oxalyl chloride (151 mg) in dichloromethane (3 ml) was added dropwise a solution of dimethylsulfoxide (123 mg) in dichloromethane (0.25 ml) at −78° C. under nitrogen atmosphere. After 15 minutes, (2R)-1-[3,5-bis(trifluoromethyl)benzoyl]-2-(3,4-dimethylbenzyl)-4-[2-(2-hydroxyethoxy)ethyl]piperazine (317 mg) was added at the same temperature. After 15 minutes, the resulting mixture was stirred at −45° C. for 1 hour. Triethylamine (446 mg) was added at −45° C., and the whole was stirred at 0° C. for 20 minutes and then treated with aqueous solution of ammonium chloride (2 ml). The organic layer was separated and dried over magnesium sulfate. After evaporation of the solvent, the resulting residue was purified by column chromatography on silica gel using ethyl acetate as eluent to afford (2R)-1-[3,5-bis(trifluoromethyl)benzoyl]-2-(3,4-dimethylbenzyl)-4-[2-(formylmethoxy)ethyl]piperazine (171 mg).

Workup

  1. waitAfter 15 minutes
  2. stirringthe whole was stirred at 0° C. for 20 minutes
  3. customThe organic layer was separated
  4. dry with materialdried over magnesium sulfate
  5. customAfter evaporation of the solvent
  6. customthe resulting residue was purified by column chromatography on silica gel

Sources & evidence

ORD record
ord-7a9a750feb5841668c085edf57e4a09e
Source dataset
uspto-grants-2005_08
Patent number
US06924278B2

Reaction notes

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