Sodium hydride → HCID 67388458, compound

HRID 908391Notes

Reaction equation

HRID 908391 reaction equation
[H-].[Na+].Cl.[Br:4][C:5]1[CH:9]=[N:8][NH:7][C:6]=1[O:10][CH3:11].CS(O[CH:17]1[CH2:22][CH2:21][N:20]([C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24])[CH2:19][CH2:18]1)(=O)=O>CN(C=O)C>[Br:4][C:5]1[C:6]([O:10][CH3:11])=[N:7][N:8]([CH:17]2[CH2:22][CH2:21][N:20]([C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24])[CH2:19][CH2:18]2)[CH:9]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 41848691-(tert-Butoxycarbonyl)-4-(methanesulfonyloxy)piperidineHCID 131729177HCID 131729177, compound

Product 1

HCID 67388458HCID 67388458, compoundYield 52.6%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Sodium hydride (354 mg, 60% dispersion in oil) was added portionwise to a solution of 4-bromo-3-methoxy-2H-pyrazole, hydrochloride salt (755 mg) in degassed DMF (12 ml) under argon at room temperature. The resulting suspension was stirred at room temperature for 10 minutes. tert-butyl 4-methylsulphonyloxypiperidine-1-carboxylate (1.087 g) was added to the stirred suspension. The resulting mixture was stirred at 90° C. for 20 hours. The reaction mixture was allowed to cool to room temperature, quenched with water, diluted with ethyl acetate then water and extracted with ethyl acetate. The combined organic phases were washed with brine, dried over magnesium sulfate and concentrated. The residue was purified by flash chromatography on silica gel eluting with 0 to 20% ethyl acetate in petroleum ether. The solvent was evaporated to dryness to afford tert-butyl 4-(4-bromo-3-methoxy-pyrazol-1-yl)piperidine-1-carboxylate (670 mg). NMR Spectrum: (CDCl3) 1.47 (s, 9H), 1.78 (dd, 1H), 1.83 (dd, 1H), 2.03-2.10 (m, 2H), 2.78-2.93 (m, 2H), 3.93 (s, 3H), 3.99-4.07 (m, 1H), 4.13-4.31 (m, 2H), 7.24 (s, 1H)

Workup

  1. stirringThe resulting mixture was stirred at 90° C. for 20 hours
  2. temperatureto cool to room temperature
  3. customquenched with water
  4. additiondiluted with ethyl acetate
  5. extractionwater and extracted with ethyl acetate
  6. washThe combined organic phases were washed with brine
  7. dry with materialdried over magnesium sulfate
  8. concentrationconcentrated
  9. customThe residue was purified by flash chromatography on silica gel eluting with 0 to 20% ethyl acetate in petroleum ether
  10. customThe solvent was evaporated to dryness

Sources & evidence

ORD record
ord-6076179e273f4cb9b0763b6924e850d7
Source dataset
uspto-grants-2011_09
Patent number
US08017611B2

Reaction notes

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