Sodium Hydroxide → HCID 6927049, compound

HRID 1375037Notes

Reaction equation

HRID 1375037 reaction equation
[H-].[Al+3].[Li+].[H-].[H-].[H-].[CH2:7]([N:14]1[CH2:19][C:18](=[O:20])[NH:17][C@H:16]([CH2:21][C:22]2[CH:27]=[CH:26][C:25]([OH:28])=[C:24]([O:29][CH3:30])[CH:23]=2)[C:15]1=O)[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1.[OH-].[Na+].[F:34][C:35]([F:50])([F:49])[C:36]1[CH:37]=[C:38]([CH:42]=[C:43]([C:45]([F:48])([F:47])[F:46])[CH:44]=1)[C:39](Cl)=[O:40]>O1CCCC1.O>[CH2:7]([N:14]1[CH2:19][CH2:18][N:17]([C:39](=[O:40])[C:38]2[CH:37]=[C:36]([C:35]([F:50])([F:49])[F:34])[CH:44]=[C:43]([C:45]([F:48])([F:47])[F:46])[CH:42]=2)[C@H:16]([CH2:21][C:22]2[CH:27]=[CH:26][C:25]([OH:28])=[C:24]([O:29][CH3:30])[CH:23]=2)[CH2:15]1)[C:8]1[CH:9]=[CH:10][CH:11]=[CH:12][CH:13]=1.[F:34][C:35]([F:50])([F:49])[C:36]1[CH:37]=[C:38]([CH:42]=[C:43]([C:45]([F:48])([F:47])[F:46])[CH:44]=1)[C:39]([O-:20])=[O:40]

Participants

8

Reactant 4

HCID 14798Sodium HydroxideHCID 1018563,5-Bis(trifluoromethyl)benzoyl chlorideHCID 21226445Aluminium lithium hydrideHCID 54282180HCID 54282180, compound

Product 2

HCID 6927049HCID 6927049, compoundHCID 54006018HCID 54006018, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

Lithium aluminum hydride (614 mg) was added to a suspension of (3R)-1-benzyl-3-(4-hydroxy-3-methoxybenzyl)piperazine-2,5-dione (1.1 g) in tetrahydrofuran (40 ml) at room temperature. After being stirred under reflux for 5 hours, the reaction mixture was treated with 2N sodium hydroxide (5 ml) under nitrogen atmosphere. The whole mixture was diluted with water (40 ml) and thereto 3,5-bis(trifluoromethyl)benzoyl chloride (1.6 ml) was added dropwise under ice-cooling. After being stirred for 30 minutes, the resulting mixture was extracted with ethyl acetate. The organic layer was separated, dried over magnesium sulfate and evaporated under reduced pressure. The residue was purified by column chromatography on silica gel using a mixture of hexane and ethyl acetate (4:1) to give the objective (2R)-4-benzyl-1-[3,5-bis(trifluoromethyl)benzoyl]-2-(4-hydroxy-3-methoxybenzyl)piperazine and its 3,5-bis(trifluoromethyl)benzoate, which was converted to the objective compound by treatment with a mixture of 1N sodium hydroxide and methanol.

Workup

  1. temperatureunder reflux for 5 hours
  2. temperaturecooling
  3. stirringAfter being stirred for 30 minutes
  4. extractionthe resulting mixture was extracted with ethyl acetate
  5. customThe organic layer was separated
  6. dry with materialdried over magnesium sulfate
  7. customevaporated under reduced pressure
  8. customThe residue was purified by column chromatography on silica gel using
  9. additiona mixture of hexane and ethyl acetate (4:1)

Sources & evidence

ORD record
ord-08e4a5229d2344fd87dc325901a0f83e
Source dataset
uspto-grants-2007_01
Patent number
US07166598B2

Reaction notes

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