4-Bromopyrazole → Tert-butyl 4-(4-bromopyrazol-1-yl)-4-(cyanomethyl)piperidine-1-carboxylate

HRID 908389Notes

Reaction equation

HRID 908389 reaction equation
[Br:1][C:2]1[CH:3]=[N:4][NH:5][CH:6]=1.N12CCCN=C1CCCCC2.[C:18]([CH:20]=[C:21]1[CH2:26][CH2:25][N:24]([C:27]([O:29][C:30]([CH3:33])([CH3:32])[CH3:31])=[O:28])[CH2:23][CH2:22]1)#[N:19]>C(#N)C>[Br:1][C:2]1[CH:3]=[N:4][N:5]([C:21]2([CH2:20][C:18]#[N:19])[CH2:22][CH2:23][N:24]([C:27]([O:29][C:30]([CH3:31])([CH3:32])[CH3:33])=[O:28])[CH2:25][CH2:26]2)[CH:6]=1

Participants

5

Reactant 3

HCID 163754-BromopyrazoleHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 15326949tert-Butyl 4-(cyanomethylidene)piperidine-1-carboxylate

Product 1

HCID 67388489Tert-butyl 4-(4-bromopyrazol-1-yl)-4-(cyanomethyl)piperidine-1-carboxylateYield 62.7%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

4-bromo-1H-pyrazole (362 mg), 1,8-diazabicyclo[5.4.0]undec-7-ene (0.368 ml) and tert-butyl 4-(cyanomethylene)piperidine-1-carboxylate (547 mg) in acetonitrile (10 ml) were stirred at 45° C. for 6 hours. The crude reaction was concentrated on dicalite (diatomaceous earth) and 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-bromopyrazol-1-yl)-4-(cyanomethyl)piperidine-1-carboxylate (570 mg) as a white foam. NMR Spectrum: (DMSO-d6) 1.45 (s, 9H), 1.94-2.04 (m, 2H), 2.54-2.62 (m, 2H), 2.80 (s, 2H), 2.93-3.04 (m, 2H), 3.88 (bs, 2H), 7.57 (s, 1H), 7.73 (s, 1H)

Workup

  1. customThe crude reaction
  2. concentrationwas concentrated on dicalite (diatomaceous earth)
  3. customwas purified by flash chromatography on silica gel eluting with 0 to 20% ethyl acetate in petroleum ether
  4. customThe solvent was evaporated to dryness

Sources & evidence

ORD record
ord-672d54d81b954e0b917126cbde203c45
Source dataset
uspto-grants-2011_09
Patent number
US08017611B2

Reaction notes

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