2-Fluoropyridine → benzyl 4-(2-fluoropyridin-3-yl)-4-hydroxypiperidine-1-carboxylate
Reaction equation
C([N-]C(C)C)(C)C.[Li+].[F:9][C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][N:11]=1.[Br-].[Li+].[CH2:18]([O:25][C:26]([N:28]1[CH2:33][CH2:32][C:31](=[O:34])[CH2:30][CH2:29]1)=[O:27])[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1>O1CCCC1.O.CCCCCC>[CH2:18]([O:25][C:26]([N:28]1[CH2:33][CH2:32][C:31]([OH:34])([C:15]2[C:10]([F:9])=[N:11][CH:12]=[CH:13][CH:14]=2)[CH2:30][CH2:29]1)=[O:27])[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1Participants
Reactant 4
Product 1
Reagents, catalysts & solvents 3
Conditions
- Temperature
- -50 °C
Procedure
To a solution of lithium diisopropylamide (0.31 mol) in 300 mL of anhydrous tetrahydrofuran:hexane at -78° C. was added a solution of 2-fluoropyridine (24.6 mL) in 40 mL of anhydrous tetrahydrofuran. The reaction mixture was allowed to warm to -50° C., cooled back to -74° C. and treated dropwise with a solution of lithium bromide (55.5 g) and 1-benzyloxycarbonyl-4-oxopiperidine (55.5 g) in 300 mL of anhydrous tetrahydrofuran so that the temperature of the reaction mixture remained below -70° C. After the addition was complete, the reaction mixture was allowed to warm to -30° C. and then treated with water. The organic layer was separated and the aqueous layer was extracted with two portions of ether. Combined organic layers were dried and evaporated to afford the crude product. This material was purified by column chromatography to afford the pure product.
Workup
- temperaturecooled back to -74° C.
- customremained below -70° C
- additionAfter the addition
- temperatureto warm to -30° C.
- customThe organic layer was separated
- extractionthe aqueous layer was extracted with two portions of ether
- customCombined organic layers were dried
- customevaporated
Sources & evidence
- ORD record
- ord-18d71a69368e48e4b1b44523334e0e52
- Source dataset
- uspto-grants-1997_08
- Patent number
- US05654299
Reaction notes
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