Hydrazine hydrate (1:1) → 5-(4-(4-Cyanophenyl)-4-fluoropiperidine-1-carbonyl)-2-cyclobutyl-4-ethylbenzohydrazide

HRID 541352Notes

Reaction equation

HRID 541352 reaction equation
[C:1]([C:3]1[CH:8]=[CH:7][C:6]([C:9]2([F:33])[CH2:14][CH2:13][N:12]([C:15]([C:17]3[C:18]([CH2:31][CH3:32])=[CH:19][C:20]([CH:27]4[CH2:30][CH2:29][CH2:28]4)=[C:21]([CH:26]=3)[C:22](OC)=[O:23])=[O:16])[CH2:11][CH2:10]2)=[CH:5][CH:4]=1)#[N:2].O.[NH2:35][NH2:36]>C(O)C>[C:1]([C:3]1[CH:8]=[CH:7][C:6]([C:9]2([F:33])[CH2:14][CH2:13][N:12]([C:15]([C:17]3[C:18]([CH2:31][CH3:32])=[CH:19][C:20]([CH:27]4[CH2:30][CH2:29][CH2:28]4)=[C:21]([CH:26]=3)[C:22]([NH:35][NH2:36])=[O:23])=[O:16])[CH2:11][CH2:10]2)=[CH:5][CH:4]=1)#[N:2]

Participants

4

Reactant 2

HCID 24654Hydrazine hydrate (1:1)HCID 68288689Methyl 5-(4-(4-cyanophenyl)-4-fluoropiperidine-1-carbonyl)-2-cyclobutyl-4-ethylbenzoate2×

Product 1

HCID 682891365-(4-(4-Cyanophenyl)-4-fluoropiperidine-1-carbonyl)-2-cyclobutyl-4-ethylbenzohydrazideYield 82%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
80 °C

Procedure

To a round-bottom flask was added a solution of methyl 5-(4-(4-cyanophenyl)-4-fluoropiperidine-1-carbonyl)-2-cyclobutyl-4-ethylbenzoate (compound 217.1, 1.10 g, 2.45 mmol, 1.00 equiv) in ethanol (40 mL). Hydrazine hydrate (20 mL) was added to the reaction mixture, and the reaction was stirred 80° C. for 15 h. After cooling to ambient temperature, the mixture was concentrated in vacuo, then diluted with 50 mL of H2O. The resulting mixture was extracted with 3×50 mL of dichloromethane. The combined organic layers were washed with 2×50 mL of brine, dried over anhydrous sodium sulfate, and concentrated in vacuo. The residue was purified using silica gel column chromatography with ethyl acetate/petroleum ether (1:1-1:0) as eluent to yield 900 mg (82%) of 5-(4-(4-cyanophenyl)-4-fluoropiperidine-1-carbonyl)-2-cyclobutyl-4-ethylbenzohydrazide as a white solid.

Workup

  1. temperatureAfter cooling to ambient temperature
  2. concentrationthe mixture was concentrated in vacuo
  3. additiondiluted with 50 mL of H2O
  4. extractionThe resulting mixture was extracted with 3×50 mL of dichloromethane
  5. washThe combined organic layers were washed with 2×50 mL of brine
  6. dry with materialdried over anhydrous sodium sulfate
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified

Sources & evidence

ORD record
ord-f5607eeb06e244368ea2c55c3241d660
Source dataset
uspto-grants-2014_10
Patent number
US08871790B2

Reaction notes

Loading…