Sodium hydride → (2R,5S)-4-Benzyl-2-methyl-5-(3-oxo-morpholin-4-ylmethyl)-piperazine-1-carboxylic acid tert-butyl ester

HRID 1475473Notes

Reaction equation

HRID 1475473 reaction equation
[NH:1]1[CH2:6][CH2:5][O:4][CH2:3][C:2]1=[O:7].[H-].[Na+].[C:10]([O:14][C:15]([N:17]1[CH2:22][C@H:21]([CH2:23]Cl)[N:20]([CH2:25][C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)[CH2:19][C@H:18]1[CH3:32])=[O:16])([CH3:13])([CH3:12])[CH3:11]>CN(C=O)C>[C:10]([O:14][C:15]([N:17]1[CH2:22][C@H:21]([CH2:23][N:1]2[CH2:6][CH2:5][O:4][CH2:3][C:2]2=[O:7])[N:20]([CH2:25][C:26]2[CH:27]=[CH:28][CH:29]=[CH:30][CH:31]=2)[CH2:19][C@H:18]1[CH3:32])=[O:16])([CH3:11])([CH3:12])[CH3:13]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 669533-MorpholinoneHCID 86724019tert-butyl (2R,5R)-4-benzyl-5-(chloromethyl)-2-methylpiperazine-1-carboxylate

Product 1

HCID 70980162(2R,5S)-4-Benzyl-2-methyl-5-(3-oxo-morpholin-4-ylmethyl)-piperazine-1-carboxylic acid tert-butyl esterYield 73.9%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

Morpholin-3-one (896 mg, 8.87 mmol) was added to a slurry of NaH (60% in mineral oil, 355 mg, 8.87 mmol) in DMF (10 mL) under N2. The suspension was stirred for 30 minutes at room temperature and then a solution of (2R,5R)-4-benzyl-5-chloromethyl-2-methyl-piperazine-1-carboxylic acid tert-butyl ester (2.0 g, 5.9 mmol) in DMF (10 mL) was slowly added. The resulting mixture was stirred at 65° C. for 2 h. The reaction was cooled to room temperature and partitioned between EtOAc and saturated aqueous NaHCO3. The organic phase was dried over MgSO4 and concentrated in vacuo. Chromatography (50% EtOAc in petrol) gave the title compound (1.76 g) as a pale yellow gum. MS: [M+H]+=404.

Workup

  1. stirringThe resulting mixture was stirred at 65° C. for 2 h
  2. temperatureThe reaction was cooled to room temperature
  3. custompartitioned between EtOAc and saturated aqueous NaHCO3
  4. dry with materialThe organic phase was dried over MgSO4
  5. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-eb6113c5aef741abab9fbcc34ca8eda6
Source dataset
uspto-grants-2015_04
Patent number
US09018214B2

Reaction notes

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