2-Nitropropane → Methyl 2-(4-chlorophenyl)-4-methyl-4-nitropentanoate
Reaction equation
N12CCCN=C1CCCCC2.[Cl:12][C:13]1[CH:18]=[CH:17][C:16]([C:19](=[CH2:24])[C:20]([O:22][CH3:23])=[O:21])=[CH:15][CH:14]=1.[N+:25]([CH:28]([CH3:30])[CH3:29])([O-:27])=[O:26]>CC#N>[Cl:12][C:13]1[CH:14]=[CH:15][C:16]([CH:19]([CH2:24][C:28]([CH3:30])([N+:25]([O-:27])=[O:26])[CH3:29])[C:20]([O:22][CH3:23])=[O:21])=[CH:17][CH:18]=1Participants
Procedure
1,8-Diazabicyclo[5.4.0]undec-7-ene (33.68 ml, 225.2 mmol) was added to a solution of methyl 2-(4-chlorophenyl)acrylate (36.9 g, 187.7 mmol) and 2-nitropropane (20.23 ml, 225.2 mmol) in CH3CN (500 mL) at 0° C. under nitrogen. The reaction mixture was warmed to room temperature and stirred overnight. The solution was concentrated in vacuo and subjected to column chromatography (20% EtOAc/hexane) to give methyl 2-(4-chlorophenyl)-4-methyl-4-nitropentanoate (52.9 g, 98.66% yield) as a colorless oil. Concentrated HCl (10 ml) was added dropwise over 2 minutes to a suspension of the methyl 2-(4-chlorophenyl)-4-methyl-4-nitropentanoate (10 g, 35.0 mmol) and zinc (6.41 ml, 700 mmol) in EtOH (250 mL) at 40° C. The suspension was stirred at 40° C. overnight. LCMS shows desired product and reduced (but non-cyclized) product. The temperature was increased to 50° C. for 8 hours. There was no change by LCMS, so the reaction mixture was diluted with EtOAc (200 ml) and filtered. The filtrate was concentrated in vacuo, taken up into EtOAc/EtOH (500 ml, 9:1), washed with bicarbonate solution, dried over Na2SO4 and concentrated in vacuo. The crude product contained 2-3 compounds, however, the 3-(4-chlorophenyl)-5,5-dimethylpyrrolidin-2-one (6.7 g, 85.6% yield) was the major one. Used as-is in the next step. LCMS (APCI+) [M-Boc+H]+ 224.1; Rt: 2.90 min.
Workup
- concentrationThe solution was concentrated in vacuo
Sources & evidence
- ORD record
- ord-82bf0358a499417fa2ce7520d0c9905d
- Source dataset
- uspto-grants-2016_04
- Patent number
- US09303040B2
Reaction notes
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