Sodium hydride → HCID 59718568, compound

HRID 423506Notes

Reaction equation

HRID 423506 reaction equation
[C:1]([N:8]1[CH2:13][CH2:12][CH:11]([CH2:14][OH:15])[CH2:10][CH2:9]1)([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].[H-].[Na+].Br[C:19]1[CH:24]=[CH:23][C:22]([Br:25])=[CH:21][N:20]=1>CS(C)=O.O>[Br:25][C:22]1[CH:23]=[CH:24][C:19]([O:15][CH2:14][CH:11]2[CH2:12][CH2:13][N:8]([C:1]([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2])[CH2:9][CH2:10]2)=[N:20][CH:21]=1

Participants

6

Reactant 3

HCID 24758Sodium hydrideHCID 693532,5-DibromopyridineHCID 2764081Tert-butyl 4-(hydroxymethyl)piperidine-1-carboxylate

Product 1

HCID 59718568HCID 59718568, compoundYield 84%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolvent3×HCID 962WaterSolvent

Procedure

A solution of N-Boc-4-piperidinemethanol (1.0 g, 4.50 mmol) in DMSO (2 mL) was added dropwise to a suspension of NaH (60% dispersion in mineral oil, 0.27 g, 6.76 mmol) in DMSO (4 mL). The mixture was stirred at ambient temperature for 1 h, then 30 minutes at 50° C. The mixture was allowed to cool to ambient temperature, and a solution of 2,5-dibromopyridine (1.12 g, 4.73 mmol) in DMSO (4 mL) was added dropwise, and the reaction mixture was stirred at ambient temperature overnight, poured in water, then extracted with EtOAc. The organic extract was washed with water and brine, dried over Na2SO4, filtered, and the filtrate was concentrated to give the crude product as an amber oil. The crude product was purified by chromatography on a silica gel column eluted with 1:8 EtOAc/hexane to give 1.40 g (84%) of 1,1-dimethylethyl 4-{[(5-bromo-2-pyridinyl)oxy]methyl}-1-piperidinecarboxylate as a white solid after standing. 1H NMR (400 MHz, CDCl3): δ 8.16 (d, 1H, J=2.2 Hz), 7.64 (dd, 1H, Ja=8.7 Hz, Jb=2.3 Hz), 6.64 (d, 1H, J=8.8 Hz), 7.04 (d, 2H, J=8.8 Hz), 4.20-4.10 (m, 4H), 2.80-2.65 (m, 2H), 2.00-1.85 (m, 1H), 1.85-1.70 (m, 2H), 1.45 (s, 9H), 1.30-1.20 (m, 2H); LRMS (ESI), m/z 371/373 (M+H).

Workup

  1. custom30 minutes
  2. customat 50° C
  3. temperatureto cool to ambient temperature
  4. stirringthe reaction mixture was stirred at ambient temperature overnight
  5. extractionextracted with EtOAc
  6. extractionThe organic extract
  7. washwas washed with water and brine
  8. dry with materialdried over Na2SO4
  9. filtrationfiltered
  10. concentrationthe filtrate was concentrated
  11. customto give the crude product as an amber oil
  12. customThe crude product was purified by chromatography on a silica gel column
  13. washeluted with 1:8 EtOAc/hexane

Sources & evidence

ORD record
ord-c31ff8bce21b42b18c9867bdc63e6ffb
Source dataset
uspto-grants-2012_01
Patent number
US08101634B2

Reaction notes

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