Ethyl chloroacetate → (R)-5-Cyclohexyl-morpholin-3-one
Reaction equation
[NH2:1][C@H:2]([CH:5]1[CH2:10][CH2:9][CH2:8][CH2:7][CH2:6]1)[CH2:3][OH:4].[H-].[Na+].[H][H].Cl[CH2:16][C:17](OCC)=[O:18]>C1COCC1>[CH:5]1([C@H:2]2[NH:1][C:17](=[O:18])[CH2:16][O:4][CH2:3]2)[CH2:10][CH2:9][CH2:8][CH2:7][CH2:6]1Participants
Conditions
- Temperature
- 0 °C
Procedure
To a solution containing 3.8 g (26.5 mmol, 1.0 equiv) of (R)-2-amino-2-cyclohexyl-ethanol in 100 mL of THF was added sodium hydride (1.4 g, 58.4 mmol, 60% in mineral oil, 2.2 equiv). The reaction mixture was stirred at 25° C. for 30 minutes, at which time hydrogen evolution had ceased. The mixture was cooled at 0° C. and was added ethyl chloroacetate (3.3 g, 26.5 mmol, 1.0 equiv), dropwise, over 5 minutes. The reaction mixture was stirred for 1 hour at 25° C. and then 2 hours at reflux. The solvent was removed under vacuum and to the residue was added 1.0 N HCl aq. solution until pH=6. The mixture was extracted with ethyl acetate. The resulting organic extracts were washed with brine, dried over sodium sulfate and concentrated in vacuo. The residue was recrystallized from EtOAc/heptane to give product 2.8 g. The mother liquid was concentrated and the residue was purified by silica gel column chromatography (acetone/heptane 50%) to give product 1.3 g. Combined yield 4.1 g (84%)
Workup
- temperature2 hours at reflux
- customThe solvent was removed under vacuum and to the residue
- additionwas added 1.0 N HCl aq. solution until pH=6
- extractionThe mixture was extracted with ethyl acetate
- washThe resulting organic extracts were washed with brine
- dry with materialdried over sodium sulfate
- concentrationconcentrated in vacuo
- customThe residue was recrystallized from EtOAc/heptane
Sources & evidence
- ORD record
- ord-61491137d9694755840c570f0932106c
- Source dataset
- uspto-grants-2015_05
- Patent number
- US09040690B2
Reaction notes
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