2-Bromopyridine → Benzyl 4-hydroxy-4-(pyridin-2-yl)piperidine-1-carboxylate

HRID 490168Notes

Reaction equation

HRID 490168 reaction equation
Br[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][N:3]=1.[Li]CCCC.[O:13]=[C:14]1[CH2:19][CH2:18][N:17]([C:20]([O:22][CH2:23][C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)=[O:21])[CH2:16][CH2:15]1>C1COCC1>[OH:13][C:14]1([C:2]2[CH:7]=[CH:6][CH:5]=[CH:4][N:3]=2)[CH2:15][CH2:16][N:17]([C:20]([O:22][CH2:23][C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)=[O:21])[CH2:18][CH2:19]1

Participants

5

Reactant 3

HCID 79732-BromopyridineHCID 643496Benzyl 4-oxopiperidine-1-carboxylateHCID 178418339Butyllithium

Product 1

HCID 22221502Benzyl 4-hydroxy-4-(pyridin-2-yl)piperidine-1-carboxylateYield 27%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-60 °C

Procedure

2-Bromopyridine (0.470 mL, 5 mmol) in THF (20 mL) was treated with n-BuLi 1.6M in hexanes (5.2 ml, 5.2 mmol) dropwise at −60° C. After stirring at -60° C. for 30 minutes, the reaction mixture and treated with benzyl 4-oxo-1-piperidinecarboxylate (1.14 g, 4.9 mmol) in THF (10 mL) slowly. After stirring an additional 15 minutes at −60° C., the reaction mixture was quenched with a saturated aqueous solution of NH4Cl, allowed to warm to room temperature and was extracted into dichloromethane. The organics were combined, dried on MgSO4, filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by flash chromatography on silica gel (elution with hexanes:ethyl acetate, 1:1) to provide the title compound (400 mg, 27% yield). 1H NMR (300 MHz, DMSO-d6) δ 1.54 (m, 2H), 2.05 (m, 2H), 3.25 (m, 2H), 3.95 (m, 2H), 5.11 (s, 2H), 5.35 (s, 1H), 7.25 (m, 1H), 7.35 (m, 5H), 7.68 (m, 1H), 7.79 (m, 1H), 8.5 (m, 1H); MS (DCI/NH3) m/e 313 (M+H)+.

Workup

  1. stirringAfter stirring an additional 15 minutes at −60° C.
  2. customthe reaction mixture was quenched with a saturated aqueous solution of NH4Cl
  3. temperatureto warm to room temperature
  4. extractionwas extracted into dichloromethane
  5. customdried on MgSO4
  6. filtrationfiltered
  7. concentrationthe filtrate was concentrated under reduced pressure
  8. customThe residue was purified by flash chromatography on silica gel (elution with hexanes:ethyl acetate, 1:1)

Sources & evidence

ORD record
ord-3b620536ed764cd7b9fc8b5d0403b320
Source dataset
uspto-grants-2009_05
Patent number
US07528134B2

Reaction notes

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