2-Bromopyridine → Benzyl 4-hydroxy-4-(pyridin-2-yl)piperidine-1-carboxylate
Reaction equation
Br[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][N:3]=1.C([Li])(C)(C)C.[CH2:13]([O:20][C:21]([N:23]1[CH2:28][CH2:27][C:26](=[O:29])[CH2:25][CH2:24]1)=[O:22])[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1.[Cl-].[NH4+]>O1CCCC1>[CH2:13]([O:20][C:21]([N:23]1[CH2:28][CH2:27][C:26]([OH:29])([C:2]2[CH:7]=[CH:6][CH:5]=[CH:4][N:3]=2)[CH2:25][CH2:24]1)=[O:22])[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1Participants
Conditions
- Temperature
- -78 °C
Procedure
To a solution of 2-bromopyridine (1.58 g) in 50 mL of anhydrous tetrahydrofuran at -78° C. was added tert-butyl lithium (6.5 mL of 1.7M) and the reaction mixture was stirred at -78° C. for 1 hour. At the end of this period, a solution of 1-benzyloxycarbonyl-4-oxopiperidine (2.34 g) in 20 mL of anhydrous tetrahydrofuran was added and the reaction mixture was allowed to stir at -78° C. for an additional 1 hour. Upon warming the reaction mixture to room temperature, aqueous ammonium chloride was added and the resulting mixture was extracted with ethyl acetate. The organic layer was washed with sodium chloride, dried over magnesium sulfate and evaporated to afford the crude product. This a material was purified by column chromatography; elution with 1:1 hexane:ethyl acetate afforded the named product (1.0 g); MS: 313; NMR: 6.63 (m, 3), 1.94 (m, 2), 3.37 (m, 2), 4.13 (m, 2).
Workup
- stirringto stir at -78° C. for an additional 1 hour
- temperatureUpon warming the reaction mixture to room temperature
- extractionthe resulting mixture was extracted with ethyl acetate
- washThe organic layer was washed with sodium chloride
- dry with materialdried over magnesium sulfate
- customevaporated
- customto afford the crude product
- customThis a material was purified by column chromatography
- washelution with 1:1 hexane
Sources & evidence
- ORD record
- ord-d20bb18f901c4222af7fb242faf6ba4b
- Source dataset
- uspto-grants-1997_08
- Patent number
- US05654299
Reaction notes
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