Water → tert-Butyl 4-(2-ethoxy-2-oxoethylidene)piperidine-1-carboxylate
Reaction equation
O=[C:2]1[CH2:7][CH2:6][N:5]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[CH2:4][CH2:3]1.[H-].[Na+].[OH2:17].[CH2:18]1[CH2:22][O:21][CH2:20][CH2:19]1>>[CH2:20]([O:21][C:22](=[O:17])[CH:18]=[C:2]1[CH2:7][CH2:6][N:5]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[CH2:4][CH2:3]1)[CH3:19]Participants
Procedure
A solution of tert-butyl 4-oxopiperidine-1-carboxylate (10.0 g, 50.25 mmol, 1 eq) in THF (50 ml) was slowly added dropwise to an ice-cold (0° C.) suspension of NaH (1.56 g, 65.32 mmol, 1.3 eq) in THF (50 ml), and stirring was carried out for 30 min. Triethyl phosphonoacetate (12.96 ml, 65.32 mmol, 1.3 eq), dissolved in THF (50 ml), was added and stirring was carried out for 2 h at RT. The reaction mixture was hydrolyzed with water (5 ml) and concentrated. The residue was taken up in water (150 ml) and extracted with ethyl acetate (2×300 ml). The combined organic phases were washed with sat. NaCl solution (200 ml), dried over sodium sulfate and concentrated under reduced pressure. After purification by column chromatography (silica gel, 3% ethyl acetate in hexane), the desired product was obtained in the form of a white solid. Yield: 78% (10.5 g, 39.03 mmol).
Workup
- additionwas added
- stirringstirring
- waitwas carried out for 2 h at RT
- concentrationconcentrated
- extractionextracted with ethyl acetate (2×300 ml)
- washThe combined organic phases were washed with sat. NaCl solution (200 ml)
- dry with materialdried over sodium sulfate
- concentrationconcentrated under reduced pressure
- customAfter purification by column chromatography (silica gel, 3% ethyl acetate in hexane)
Sources & evidence
- ORD record
- ord-0334e856f81245799ce721ab7c14a794
- Source dataset
- uspto-grants-2014_03
- Patent number
- US08680159B2
Reaction notes
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