Sodium hydride → HCID 49657818, compound

HRID 423564Notes

Reaction equation

HRID 423564 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+].[Cl:18][C:19]1[N:20]=[N:21][C:22](Cl)=[CH:23][CH:24]=1>CS(C)=O>[Cl:18][C:19]1[N:20]=[N:21][C:22]([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)=[CH:23][CH:24]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 673313,6-DichloropyridazineHCID 2764081Tert-butyl 4-(hydroxymethyl)piperidine-1-carboxylate

Product 1

HCID 49657818HCID 49657818, compoundYield 57.6%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent2×

Procedure

A solution of N-Boc-4-piperidinemethanol (1.0 g, 4.50 mmol) was added dropwise to a suspension of NaH (60% in mineral oil, 0.27 g, 6.76 mmol) in DMSO (2 mL). The mixture was stirred at ambient temperature for 1 h, then 30 minutes at 50° C. The mixture was cooled to ambient temperature and a solution of 3,6-dichloropyridazine (0.73 g, 4.73 mmol) in DMSO (4 mL) was added dropwise, and the reaction mixture was stirred at ambient temperature overnight, poured onto water, then extracted with EtOAc, washed with water and brine, dried over Na2SO4, filtered, and the filtrate was concentrated to give the crude product as a dark reddish brown oil. The crude product was purified by chromatography on ISCO silica gel column eluted with a EtOAc:hexane gradient (0 to 30%) to give 0.85 g (56%) of 1,1-dimethylethyl 4-{[(6-chloro-3-pyridazinyl)oxy]methyl}-1-piperidinecarboxylate as a white solid. 1H NMR (400 MHz, CDCl3): δ 7.36 (d, 1H, J=9.0 Hz), 6.94 (d, 1H, J=9.1 Hz), 4.34 (d, 2H, J=6.6 Hz), 4.20-4.10 (m, 2H), 2.80-2.65 (m, 2H), 2.10-1.95 (m, 1H), 1.85-1.70 (m, 2H), 1.45 (s, 9H), 1.35-1.20 (m, 2H); LRMS (ESI), m/z 328 (M+H).

Workup

  1. custom30 minutes
  2. customat 50° C
  3. temperatureThe mixture was cooled to ambient temperature
  4. stirringthe reaction mixture was stirred at ambient temperature overnight
  5. additionpoured onto water
  6. extractionextracted with EtOAc
  7. washwashed with water and brine
  8. dry with materialdried over Na2SO4
  9. filtrationfiltered
  10. concentrationthe filtrate was concentrated
  11. customto give the crude product as a dark reddish brown oil
  12. customThe crude product was purified by chromatography on ISCO silica gel column
  13. washeluted with a EtOAc

Sources & evidence

ORD record
ord-a274718292c94d31b60d9c505feda622
Source dataset
uspto-grants-2012_01
Patent number
US08101634B2

Reaction notes

Loading…