Hydrochloric Acid → benzyl 3-(1H-pyrazol-5-yl)piperidine-1-carboxylate

HRID 659605Notes

Reaction equation

HRID 659605 reaction equation
C[N:2](C)/[CH:3]=[CH:4]/[C:5]([CH:7]1[CH2:12][CH2:11][CH2:10][N:9]([C:13]([O:15][CH2:16][C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)=[O:14])[CH2:8]1)=O.Cl.[NH2:25]N.O.CCOC(C)=O>C(O)C>[NH:25]1[C:5]([CH:7]2[CH2:12][CH2:11][CH2:10][N:9]([C:13]([O:15][CH2:16][C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=3)=[O:14])[CH2:8]2)=[CH:4][CH:3]=[N:2]1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 8857Ethyl AcetateHCID 24654Hydrazine hydrate (1:1)HCID 70642147(E)-benzyl 3-(3-(dimethylamino)acryloyl)piperidine-1-carboxylate

Product 1

HCID 67996407benzyl 3-(1H-pyrazol-5-yl)piperidine-1-carboxylateYield 80%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

A 250-mL round-bottom flask was charged with a solution of (E)-benzyl 3-(3-(dimethylamino)acryloyl)piperidine-1-carboxylate (19 g, 54.05 mmol, 1.00 equiv, 90%) in ethanol (100 mL). To this was added conc.HCl (3 mL, 36%) drop wise and allowed to stir for 10 minutes. Then, to the resulting mixture was added NH2NH2.H2O (60 mL, 80%) and refluxed overnight. The progress was monitored by TLC (EtOAc:PE=1:1). Upon completion, the resulting mixture was concentrated on a rotary evaporator and diluted with H2O (200 mL). The mixture was extracted with ethyl acetate (3×200 mL). Combined organic layers were dried over anhydrous magnesium sulfate, filtered off and concentrated on a rotary evaporator affording a residue that was purified by a silica gel column chromatography eluted with ethyl acetate/petroleum ether (2:3) to give benzyl 3-(1H-pyrazol-5-yl)piperidine-1-carboxylate as colorless oil (13 g, 80%).

Workup

  1. additionTo this was added conc
  2. temperaturerefluxed overnight
  3. concentrationUpon completion, the resulting mixture was concentrated on a rotary evaporator
  4. additiondiluted with H2O (200 mL)
  5. extractionThe mixture was extracted with ethyl acetate (3×200 mL)
  6. dry with materialCombined organic layers were dried over anhydrous magnesium sulfate
  7. filtrationfiltered off
  8. concentrationconcentrated on a rotary evaporator
  9. customaffording a residue that
  10. customwas purified by a silica gel column chromatography
  11. washeluted with ethyl acetate/petroleum ether (2:3)

Sources & evidence

ORD record
ord-ee3d85c1505642f8aeecd4654da01a15
Source dataset
uspto-grants-2011_12
Patent number
US08080566B1

Reaction notes

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