Sodium Hydroxide → HCID 12016230, compound

HRID 1765990Notes

Reaction equation

HRID 1765990 reaction equation
[CH2:1]([N:8]1[CH2:13][C:12](=O)[NH:11][C@H:10]([CH2:15][C:16]2[CH:21]=[CH:20][C:19]([CH3:22])=[C:18]([O:23][CH3:24])[CH:17]=2)[C:9]1=O)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[H-].[Al+3].[Li+].[H-].[H-].[H-].[OH-].[Na+]>O1CCCC1>[CH2:1]([N:8]1[CH2:13][CH2:12][NH:11][C@H:10]([CH2:15][C:16]2[CH:21]=[CH:20][C:19]([CH3:22])=[C:18]([O:23][CH3:24])[CH:17]=2)[CH2:9]1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

5

Reactant 3

HCID 14798Sodium HydroxideHCID 12016229HCID 12016229, compoundHCID 21226445Aluminium lithium hydride

Product 1

HCID 12016230HCID 12016230, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To an ice-cooled suspension of (3R)-1-benzyl-3-(3-methoxy-4-methylbenzyl)piperazine-2,5-dione (1.35 g) in tetrahydrofuran (22 ml) was added lithium aluminum hydride (0.378 g) at 5° C. or below under a nitrogen atmosphere. The mixture was stirred under reflux for 3 hours. After cooling the mixture to 5° C. or below, 2N sodium hydroxide was added to the mixture. After stirring the mixture for 30 minutes, insoluble matters were collected by filtration and washed with tetrahydrofuran. The filtrate and the washings were combined and the solvent was evaporated under reduced pressure to give (3R)-1-benzyl-3-(3-methoxy-4-methylbenzyl)piperazine in the form of an oily substance. A solution of 3,5-bis(trifluoromethyl)benzoyl chloride (0.80 ml) in dichloromethane (1 ml) was added dropwise to an ice-cooled solution of (3R)-1-benzyl-3-(3-methoxy-4-methylbenzyl)-piperazine obtained by the above process and triethylamine (0.84 ml) in dichloromethane (10 ml) at 5° C. or below over 5 minutes. After stirring at the same temperature for 30 minutes, the reaction mixture was washed with an aqueous sodium chloride solution and dried over magnesium sulfate. The solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography using a mixed solvent of hexane and ethyl acetate (4:1). Fractions containing the desired compound were collected and the solvent was evaporated under reduced pressure to give (2R)-4-benzyl-1-[3,5-bis(trifluoromethyl)benzoyl]-2-(3-methoxy-4-methylbenzyl)-piperazine (1.92 g) in the form of an oily substance.

Workup

  1. temperatureunder reflux for 3 hours
  2. temperatureAfter cooling the mixture to 5° C. or below
  3. stirringAfter stirring the mixture for 30 minutes
  4. filtrationinsoluble matters were collected by filtration
  5. washwashed with tetrahydrofuran
  6. customthe solvent was evaporated under reduced pressure

Sources & evidence

ORD record
ord-88aacdb6c6f4490fa039539b43672422
Source dataset
uspto-grants-2007_06
Patent number
US07229992B2

Reaction notes

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