Methyl acetoacetate → Methyl 3-oxo-5-(phenylthio)pentanoate
Reaction equation
[H-].[Na+].[CH3:3][O:4][C:5](=[O:10])[CH2:6][C:7]([CH3:9])=[O:8].[Li]CCCC.Cl[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=1[S:23][CH3:24]>C1COCC1.CN(P(N(C)C)(N(C)C)=O)C.C1COCC1>[C:18]1([S:23][CH2:24][CH2:9][C:7](=[O:8])[CH2:6][C:5]([O:4][CH3:3])=[O:10])[CH:19]=[CH:20][CH:21]=[CH:22][CH:17]=1Participants
Reactant 4
Product 1
Reagents, catalysts & solvents 2
Conditions
- Temperature
- 0 °C
Procedure
To a suspension of NaH (60%) (815 mg, 20.39 mmol) in THF-HMPA (20 ml, 5 ml) was added methylacetoacetate (2.0 g, 18.5 mmol) in THF (5 ml) at 0° C. The mixture was stirred for 10 min. at 0° C. under nitrogen atmosphere. BuLi (12.3 ml, 20.39 mmol) was dropwise added and the red mixture was stirred for 15 min. at 0° C. Then a solution of chlorothioanisole (2.7 ml, 20.39 mmol) in THF (5 ml) was added to the mixture at 0° C. The mixture was stirred for 1 h at -5° C. The mixture was quenched with H2O, then extracted with AcOEt (100 ml×2). AcOEt layer was washed with H2O (10 ml×2) and brine (10 ml), then dried over MgSO4 and evaporated. The residue was purified by a silica gel column chromatography (150 g, hexane :AcOEt=6:1) to give a colorless oil (1.0 g, 22.7%).
Workup
- stirringthe red mixture was stirred for 15 min. at 0° C
- stirringThe mixture was stirred for 1 h at -5° C
- customThe mixture was quenched with H2O
- extractionextracted with AcOEt (100 ml×2)
- washAcOEt layer was washed with H2O (10 ml×2) and brine (10 ml)
- dry with materialdried over MgSO4
- customevaporated
- customThe residue was purified by a silica gel column chromatography (150 g, hexane :AcOEt=6:1)
Sources & evidence
- ORD record
- ord-0662be53814b40eda18d24f9bf08d60d
- Source dataset
- uspto-grants-2000_10
- Patent number
- US06131226
Reaction notes
Loading…