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

HRID 1061568Notes

Reaction equation

HRID 1061568 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-carboxylate

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-60 °C

Procedure

A solution of 2-bromopyridine (0.47 mL, 5 mmol) in THF (20 mL) was cooled to −60° C. and treated dropwise with nBuLi (1.6M in hexanes, 5.2 ml, 5.2 mmol). The reaction mixture was stirred for 30 minutes at −60° C. and then benzyl 4-oxo-1-piperidine carboxylate 1.14 g, 4.9 mmol) in THF (10 mL) was slowly added to the reaction mixture. The reaction mixture was stirred at −60° C. for 15 minutes and then quenched with saturated NH4Cl. The cooling bath was removed and reaction mixture was allowed to warm to room temperature. The mixture was were extracted with CH2Cl2 and the organics were dried (MgSO4), filtered and the filtrate concentrated under reduced pressure. The residue was purified by flash chromatography using hexane:ethyl acetate (1:1) to provide the title compound, 400 mg (27%). 1H NMR (d6-DMSO, 300 MHz) δ 1.54 (m, 4H), 2.05 (m, 4 H), 3.25 (m, 4H), 3.95 (m, 4H), 5.11 (s, 2H), 5.35 (s, 1H), 7.25 (m, 2H), 7.35 (m, 5H), 7.68 (m, 1H), 8.5 (m, 1H); MS (DCI/NH3) m/z 313 (M+H)+.

Workup

  1. stirringThe reaction mixture was stirred at −60° C. for 15 minutes
  2. customquenched with saturated NH4Cl
  3. customThe cooling bath was removed
  4. customreaction mixture
  5. temperatureto warm to room temperature
  6. extractionThe mixture was were extracted with CH2Cl2
  7. dry with materialthe organics were dried (MgSO4)
  8. filtrationfiltered
  9. concentrationthe filtrate concentrated under reduced pressure
  10. customThe residue was purified by flash chromatography

Sources & evidence

ORD record
ord-4b660dda85bb4b91bce5c061504d8ce2
Source dataset
uspto-grants-2005_11
Patent number
US06960589B2

Reaction notes

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