Potassium Carbonate → Tert-butyl 4-(4-bromo-3-cyanopyrazol-1-yl)piperidine-1-carboxylate

HRID 908472Notes

Reaction equation

HRID 908472 reaction equation
[Br:1][C:2]1[CH:6]=[N:5][NH:4][C:3]=1[C:7]#[N:8].C(=O)([O-])[O-].[K+].[K+].CS(O[CH:20]1[CH2:25][CH2:24][N:23]([C:26]([O:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[O:27])[CH2:22][CH2:21]1)(=O)=O>C(#N)C>[Br:1][C:2]1[C:3]([C:7]#[N:8])=[N:4][N:5]([CH:20]2[CH2:25][CH2:24][N:23]([C:26]([O:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[O:27])[CH2:22][CH2:21]2)[CH:6]=1

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 27356234-Bromo-1H-pyrazole-3-carbonitrileHCID 41848691-(tert-Butoxycarbonyl)-4-(methanesulfonyloxy)piperidine

Product 1

HCID 67388412Tert-butyl 4-(4-bromo-3-cyanopyrazol-1-yl)piperidine-1-carboxylateYield 60.7%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

4-bromo-2H-pyrazole-3-carbonitrile (500 mg), potassium carbonate (522 mg) and tert-butyl 4-methylsulfonyloxypiperidine-1-carboxylate (975 mg) in acetonitrile (15 ml) were stirred at 90° C. overnight. The mixture was concentrated and the residue was dissolved in ethylacetate, washed with water and brine, dried over magnesium sulfate and concentrated. The crude product was purified by flash chromatography on silica gel eluting with 10 to 50% ethyl acetate in petroleum ether. The solvent was evaporated to dryness to afford. tert-butyl 4-(4-bromo-3-cyano-pyrazol-1-yl)piperidine-1-carboxylate (627 mg) The product gave the following characterizing data: NMR Spectrum: (DMSOd6) 1.41 (s, 9H), 1.74 (dd, 1H), 1.78 (dd, 1H), 1.98-2.08 (m, 2H), 2.90 (bs, 2H), 3.95-4.11 (m, 2H), 4.46-4.57 (m, 1H), 8.45 (s, 1H).

Workup

  1. concentrationThe mixture was concentrated
  2. dissolutionthe residue was dissolved in ethylacetate
  3. washwashed with water and brine
  4. dry with materialdried over magnesium sulfate
  5. concentrationconcentrated
  6. customThe crude product was purified by flash chromatography on silica gel eluting with 10 to 50% ethyl acetate in petroleum ether
  7. customThe solvent was evaporated to dryness
  8. customto afford

Sources & evidence

ORD record
ord-c8043cb860c0442d9b1a214fd3838fb4
Source dataset
uspto-grants-2011_09
Patent number
US08017611B2

Reaction notes

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