Dimethyl Sulfate → Tert-butyl 4-[4-bromo-3-(methoxymethyl)pyrazol-1-yl]piperidine-1-carboxylate

HRID 908401Notes

Reaction equation

HRID 908401 reaction equation
[H-].[Na+].[Br:3][C:4]1[C:5]([CH2:22][OH:23])=[N:6][N:7]([CH:9]2[CH2:14][CH2:13][N:12]([C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[CH2:11][CH2:10]2)[CH:8]=1.S(OC)(O[CH3:28])(=O)=O>CN(C=O)C>[Br:3][C:4]1[C:5]([CH2:22][O:23][CH3:28])=[N:6][N:7]([CH:9]2[CH2:14][CH2:13][N:12]([C:15]([O:17][C:18]([CH3:20])([CH3:19])[CH3:21])=[O:16])[CH2:11][CH2:10]2)[CH:8]=1

Participants

5

Reactant 3

HCID 6497Dimethyl SulfateHCID 24758Sodium hydrideHCID 67388410Tert-butyl 4-[4-bromo-3-(hydroxymethyl)pyrazol-1-yl]piperidine-1-carboxylate

Product 1

HCID 67388042Tert-butyl 4-[4-bromo-3-(methoxymethyl)pyrazol-1-yl]piperidine-1-carboxylate

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Sodium hydride (57.7 mg, 60% in oil) was added to tert-butyl 4-[4-bromo-3-(hydroxymethyl)pyrazol-1-yl]piperidine-1-carboxylate (200 mg) dissolved in degassed DMF (2 mL) under nitrogen. The resulting solution was stirred at room temperature for 10 minutes. Dimethyl sulfate (0.068 ml) was added and the resulting solution was stirred at 25° C. for 1 hour. The reaction mixture was quenched with water and diluted with ethyl acetate. The aqueous phase was extracted with ethyl acetate. The combined organic phases were washed with a saturated aqueous solution of brine, dried over magnesium sulfate and concentrated in presence of silica gel to afford the crude, which was purified by flash chromatography on silica gel eluting with 0 to 100% ethyl acetate in petroleum ether. The solvent was evaporated to dryness to afford tert-butyl 4-[4-bromo-3-(methoxymethyl)pyrazol-1-yl]piperidine-1-carboxylate (180 mg). NMR Spectrum: (DMSOd6) 1.41 (s, 9H), 1.71 (dd, 1H), 1.76 (dd, 1H), 1.96 (bs, 1H), 1.98 (bs, 1H), 2.87 (bs, 2H), 3.22 (3H), 4.02 (bs, 2H), 4.28 (s, 2H), 4.29-4.36 (m, 1H), 8.04 (s, 1H).

Workup

  1. stirringthe resulting solution was stirred at 25° C. for 1 hour
  2. customThe reaction mixture was quenched with water
  3. additiondiluted with ethyl acetate
  4. extractionThe aqueous phase was extracted with ethyl acetate
  5. washThe combined organic phases were washed with a saturated aqueous solution of brine
  6. dry with materialdried over magnesium sulfate
  7. concentrationconcentrated in presence of silica gel
  8. customto afford the crude, which
  9. customwas purified by flash chromatography on silica gel eluting with 0 to 100% ethyl acetate in petroleum ether
  10. customThe solvent was evaporated to dryness

Sources & evidence

ORD record
ord-0760f0a8313545279e254e2a5aceb1d6
Source dataset
uspto-grants-2011_09
Patent number
US08017611B2

Reaction notes

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