Sodium hydride → HCID 67092255, compound

HRID 1020989Notes

Reaction equation

HRID 1020989 reaction equation
[H-].[Na+].[CH3:3][O:4][C:5]([C:7]1([CH2:21][OH:22])[CH2:11][C:10](=[O:12])[N:9]([C:13]2[C:18]([CH3:19])=[CH:17][CH:16]=[CH:15][C:14]=2[CH3:20])[CH2:8]1)=[O:6].[CH3:23][O:24][C:25]1[CH:30]=[CH:29][C:28]([CH2:31]Cl)=[CH:27][CH:26]=1.[NH4+].[Cl-]>C1COCC1>[CH3:3][O:4][C:5]([C:7]1([CH2:21][O:22][CH2:31][C:28]2[CH:29]=[CH:30][C:25]([O:24][CH3:23])=[CH:26][CH:27]=2)[CH2:11][C:10](=[O:12])[N:9]([C:13]2[C:18]([CH3:19])=[CH:17][CH:16]=[CH:15][C:14]=2[CH3:20])[CH2:8]1)=[O:6]

Participants

6

Reactant 4

HCID 24758Sodium hydrideHCID 25517Ammonium ChlorideHCID 699934-Methyloxybenzyl chlorideHCID 58218800HCID 58218800, compound

Product 1

HCID 67092255HCID 67092255, compoundYield 54%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

NaH (60% dispersed in mineral oil, 260 mg, 5.41 mmol) was added slowly to a cooled (0° C.) solution of 1-(2,6-dimethylphenyl)-3-hydroxymethyl-5-oxo-pyrrolidine-3-carboxylic acid methyl ester (prepared in the above examples, 1 g, 3.61 mmol) in THF (10 mL). After stirring for 5 min, PMBCl (737 μL, 5.41 mmol) was added and the resulting reaction mixture was slowly warmed to room temperature and stirred further for 2 h. Saturated aqueous NH4Cl solution (10 mL) was added, and the solution was extracted with EtOAc (3×25 mL). The combined organic layers were washed with water (30 mL), brine (30 mL), dried (Na2SO4) and evaporated. The residue was purified by flash chromatography (SiO2, 10→60% EtOAc/hexanes) to give 1-(2,6-dimethyl-phenyl)-3-(4-methoxy-benzyloxymethyl)-5-oxo-pyrrolidine-3-carboxylic acid methyl ester (767 mg, 54% yield). LC-MS: Rt (retention time): 2.37 min, MS: (ES) m/z 398.3 (M+H+).

Workup

  1. customthe resulting reaction mixture
  2. stirringstirred further for 2 h
  3. extractionthe solution was extracted with EtOAc (3×25 mL)
  4. washThe combined organic layers were washed with water (30 mL), brine (30 mL)
  5. dry with materialdried (Na2SO4)
  6. customevaporated
  7. customThe residue was purified by flash chromatography (SiO2, 10→60% EtOAc/hexanes)

Sources & evidence

ORD record
ord-e901f39e481e490e9ac6a829b92addd6
Source dataset
uspto-grants-2014_05
Patent number
US08716494B2

Reaction notes

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