Citric Acid → Trans-1-(Tert-Butoxycarbonyl)-3-Phenylpiperidine-4-Carboxylic Acid
Reaction equation
[C:1]1([C@H:7]2[C@@H:12]([C:13]([O:15]CC)=[O:14])[CH2:11][CH2:10][N:9]([C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[CH2:8]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.CC([O-])(C)C.[Na+].[OH-].[Na+].C(O)(=O)CC(CC(O)=O)(C(O)=O)O>C(O)C.O>[C:21]([O:20][C:18]([N:9]1[CH2:10][CH2:11][C@@H:12]([C:13]([OH:15])=[O:14])[C@H:7]([C:1]2[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=2)[CH2:8]1)=[O:19])([CH3:24])([CH3:22])[CH3:23]Participants
Conditions
- Temperature
- 90 °C
Procedure
To a solution of the compound (6.3 g) obtained in step 2 in ethanol (60 mL) was added tBuONa (3.63 g), and the mixture was stirred at 90° C. for 1 hr. The reaction mixture was cooled, 8N aqueous sodium hydroxide solution (60 mL) and water (60 mL) were added, and the mixture was stirred at 85° C. for 2 hr. The reaction mixture was cooled, and citric acid (51 g) was added. Ethanol was evaporated under reduced pressure, and the residue was extracted with ethyl acetate (200 mL). The organic layer was washed with water and dried, and the solvent was evaporated under reduced pressure. The residue was crystallized from ethyl acetate-IPE-hexane to give (3R*,4R*)-1-(tert-butoxycarbonyl)-3-phenylpiperidine-4-carboxylic acid (5.26 g, 91%) as a white powder.
Workup
- temperatureThe reaction mixture was cooled
- stirringthe mixture was stirred at 85° C. for 2 hr
- temperatureThe reaction mixture was cooled
- customEthanol was evaporated under reduced pressure
- extractionthe residue was extracted with ethyl acetate (200 mL)
- washThe organic layer was washed with water
- customdried
- customthe solvent was evaporated under reduced pressure
- customThe residue was crystallized from ethyl acetate-IPE-hexane
Sources & evidence
- ORD record
- ord-60fce13965904bd2a0f53936c622d1af
- Source dataset
- uspto-grants-2013_06
- Patent number
- US08470816B2
Reaction notes
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