Acetic Acid → 4-(4-Bromo-pyrazol-1-yl)-1-cyclopropyl-piperidine

HRID 216724Notes

Reaction equation

HRID 216724 reaction equation
C(O)(=O)C.[Br:5][C:6]1[CH:7]=[N:8][N:9]([CH:11]2[CH2:16][CH2:15][NH:14][CH2:13][CH2:12]2)[CH:10]=1.C(O[C:20]1(O[Si](C)(C)C)[CH2:22][CH2:21]1)C.C([BH3-])#N.[Na+]>CO>[Br:5][C:6]1[CH:7]=[N:8][N:9]([CH:11]2[CH2:16][CH2:15][N:14]([CH:20]3[CH2:22][CH2:21]3)[CH2:13][CH2:12]2)[CH:10]=1

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 2734686(1-Ethoxycyclopropoxy)trimethylsilaneHCID 5003444Sodium cyanoborohydrideHCID 521916214-(4-Bromo-1H-pyrazol-1-yl)piperidine

Product 1

HCID 593926324-(4-Bromo-pyrazol-1-yl)-1-cyclopropyl-piperidine

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
60 °C

Procedure

Acetic acid (1.258 ml, 21.98 mmol) is added dropwise, under stirring at RT, to a solution of 4-(4-Bromo-pyrazol-1-yl)-piperidine (as obtained in preparation 89, 1.686 g, 7.327 mmol) and [(1-ethoxy-1-cyclopropyl)oxy]trimethylsilane (2.210 ml, 10.99 mmol) in MeOH (20 ml). Sodium cyanoborohydride (775 mg, 11.7) is then added in one portion at RT. The mixture is then heated at 60° C. for 3 h. After cooling, the reaction mixture is concentrated in vacuo and the residue dissolved in EtOAc and diluted with saturated NaHCO3. After separation, the aqueous phase is re-extracted 3× with EtOAc. The combined organic layers are washed with brine, dried over Na2SO4, filtered and the filtrate is concentrated in vacuo. The residue is used without further purification in the next step, and afford the title compound as colorless solid, Rt=0.618 min (Acquity HPLC BEH C18, 2.1×50 mm, 1.7 micron, detection 215 nM, 0.1 min 2% CH3CN in H2O, 2% to 100% CH3CN in H2O in 1.5 min, 0.4 min 100% CH3CN+0.1% TFA, flow rate 1.0 ml/min); MS: 270 (M+1, 79Br)+

Workup

  1. temperatureAfter cooling
  2. concentrationthe reaction mixture is concentrated in vacuo
  3. dissolutionthe residue dissolved in EtOAc
  4. additiondiluted with saturated NaHCO3
  5. customAfter separation
  6. extractionthe aqueous phase is re-extracted 3× with EtOAc
  7. washThe combined organic layers are washed with brine
  8. dry with materialdried over Na2SO4
  9. filtrationfiltered
  10. concentrationthe filtrate is concentrated in vacuo
  11. customThe residue is used without further purification in the next step

Sources & evidence

ORD record
ord-b8abc4e1f60d464eb1bef7dca9883c41
Source dataset
uspto-grants-2012_06
Patent number
US08193189B2

Reaction notes

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