2-Pyrrolidone → (2R,5S)-4-Benzyl-2-methyl-5-(2-oxo-pyrrolidin-1-ylmethyl)-piperazine-1-carboxylic acid tert-butyl ester

HRID 1475433Notes

Reaction equation

HRID 1475433 reaction equation
[H-].[Na+].[NH:3]1[CH2:7][CH2:6][CH2:5][C:4]1=[O:8].[C:9]([O:13][C:14]([N:16]1[CH2:21][C@H:20]([CH2:22]Cl)[N:19]([CH2:24][C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)[CH2:18][C@H:17]1[CH3:31])=[O:15])([CH3:12])([CH3:11])[CH3:10].C(=O)(O)[O-].[Na+]>CN(C=O)C>[C:9]([O:13][C:14]([N:16]1[CH2:21][C@H:20]([CH2:22][N:3]2[CH2:7][CH2:6][CH2:5][C:4]2=[O:8])[N:19]([CH2:24][C:25]2[CH:26]=[CH:27][CH:28]=[CH:29][CH:30]=2)[CH2:18][C@H:17]1[CH3:31])=[O:15])([CH3:10])([CH3:11])[CH3:12]

Participants

6

Reactant 4

HCID 120252-PyrrolidoneHCID 24758Sodium hydrideHCID 516892Sodium BicarbonateHCID 86724019tert-butyl (2R,5R)-4-benzyl-5-(chloromethyl)-2-methylpiperazine-1-carboxylate

Product 1

HCID 70980575(2R,5S)-4-Benzyl-2-methyl-5-(2-oxo-pyrrolidin-1-ylmethyl)-piperazine-1-carboxylic acid tert-butyl esterYield 187.7%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Three separate reaction flasks were each charged with sodium hydride (60% in mineral oil, 0.486 g, 12.16 mmol) and anhydrous DMF (40.5 mL). To these, pyrrolidinone (0.924 mL, 12.16 mmol) was added dropwise. After stirring at this temperature for 30 minutes, (2R,5R)-4-benzyl-5-chloromethyl-2-methyl-piperazine-1-carboxylic acid tert-butyl ester (2.74 g, 8.11 mmol) was added to each at room temperature. The reactions were stirred at 80° C. for 4 h. The reactions were combined and saturated aqueous sodium bicarbonate was added and the mixture extracted with diethyl ether (3×). The combined organic layers were washed with brine, dried with sodium sulfate, filtered and concentrated. Chromatography (silica gel, gradient elution, 0-100%, EtOAc in petrol 40-60) gave the title compound (5.9 g), MS: [M+H]+=388.

Workup

  1. customThree separate
  2. customreaction flasks
  3. stirringThe reactions were stirred at 80° C. for 4 h
  4. extractionthe mixture extracted with diethyl ether (3×)
  5. washThe combined organic layers were washed with brine
  6. dry with materialdried with sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated
  9. washChromatography (silica gel, gradient elution, 0-100%, EtOAc in petrol 40-60)

Sources & evidence

ORD record
ord-275a194d664b40cb8ac96ccfe9b39d68
Source dataset
uspto-grants-2015_04
Patent number
US09018214B2

Reaction notes

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