Ammonium Chloride → 1-(2,6-Dimethylphenyl)-3-(2-methylallyl)-5-oxo-pyrrolidine-3-carboxylic acid methyl ester

HRID 1020983Notes

Reaction equation

HRID 1020983 reaction equation
[Li+].C[Si]([N-][Si](C)(C)C)(C)C.[CH3:11][O:12][C:13]([CH:15]1[CH2:19][C:18](=[O:20])[N:17]([C:21]2[C:26]([CH3:27])=[CH:25][CH:24]=[CH:23][C:22]=2[CH3:28])[CH2:16]1)=[O:14].Br[CH2:30][C:31]([CH3:33])=[CH2:32].[NH4+].[Cl-]>C1COCC1>[CH3:11][O:12][C:13]([C:15]1([CH2:32][C:31]([CH3:33])=[CH2:30])[CH2:19][C:18](=[O:20])[N:17]([C:21]2[C:26]([CH3:27])=[CH:25][CH:24]=[CH:23][C:22]=2[CH3:28])[CH2:16]1)=[O:14]

Participants

6

Reactant 4

HCID 25517Ammonium ChlorideHCID 3577853-Bromo-2-methyl-1-propeneHCID 2733832Lithium HexamethyldisilazideHCID 58218773Methyl 1-(2,6-dimethylphenyl)-5-oxopyrrolidine-3-carboxylate

Product 1

HCID 582187911-(2,6-Dimethylphenyl)-3-(2-methylallyl)-5-oxo-pyrrolidine-3-carboxylic acid methyl esterYield 53%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

LHMDS (1 M solution in THF, 83 mL, 83 mmol) was added slowly to a cooled (−50° C.) solution of 1-(2,6-dimethylphenyl)-5-oxo-pyrrolidine-3-carboxylic acid methyl ester (17 g, 68.83 mmol) in THF (170 mL). After 5 min, 3-bromo-2-methylpropene (13.8 mL, 136.8 mmol) was added slowly at −50° C. and the resulting reaction mixture was warmed to room temperature and stirred for 2 h. Saturated aqueous NH4Cl solution (50 mL) was added, and the aqueous was extracted with EtOAc (3×100 mL). The combined organic layers were washed with water (100 mL), brine (100 mL), dried (Na2SO4) and evaporated. The residue was purified by automated flash chromatography (SiO2, 20→60% MTBE/hexanes) to give 1-(2,6-dimethylphenyl)-3-(2-methylallyl)-5-oxo-pyrrolidine-3-carboxylic acid methyl ester (10.9 g, 53% yield). LC-MS: R, (retention time): 2.44 min, MS: (ES) m/z 302.1 (M+H+).

Workup

  1. customthe resulting reaction mixture
  2. extractionthe aqueous was extracted with EtOAc (3×100 mL)
  3. washThe combined organic layers were washed with water (100 mL), brine (100 mL)
  4. dry with materialdried (Na2SO4)
  5. customevaporated
  6. customThe residue was purified by automated flash chromatography (SiO2, 20→60% MTBE/hexanes)

Sources & evidence

ORD record
ord-3a5727400f3740a0b5ad148d435382d6
Source dataset
uspto-grants-2014_05
Patent number
US08716494B2

Reaction notes

Loading…