Hydrazine hydrate (1:1) → HCID 59651895, compound

HRID 2042606Notes

Reaction equation

HRID 2042606 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([O:14][C:15]2[C:20]([F:21])=[CH:19][C:18]([C:22](=O)[CH2:23][CH2:24][C:25](OCC)=[O:26])=[CH:17][C:16]=2[F:31])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].O.[NH2:33][NH2:34]>C(O)(C)C>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([O:14][C:15]2[C:20]([F:21])=[CH:19][C:18]([C:22]3[CH2:23][CH2:24][C:25](=[O:26])[NH:34][N:33]=3)=[CH:17][C:16]=2[F:31])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

4

Reactant 2

HCID 24654Hydrazine hydrate (1:1)HCID 59651900HCID 59651900, compound

Product 1

HCID 59651895HCID 59651895, compoundYield 14.1%

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Procedure

A mixture of 4-[4-(3-ethoxycarbonyl-propionyl)-2,6-difluoro-phenoxy]-piperidine-1-carboxylic acid tert-butyl ester (3.21 g, 7.27 mmol) and hydrazine monohydrate (0.7 mL, 14.1 mmol) in isopropanol (20 mL) was stirred at reflux overnight. Isopropanol was concentrated at reduced pressure and partitioned between saturated aqueous sodium bicarbonate solution and methylene chloride. The aqueous layer was extracted twice with methylene chloride and the combined organics was washed with brine, dried (Na2SO4), filtered, and concentrated to provide a crude material. The crude material was purified by ISCO (80 g silica gel column) chromatography using 15 to 60% EtOAc in hexane to obtain 4-[2,6-difluoro-4-(6-oxo-1,4,5,6-tetrahydro-pyridazin-3-yl)-phenoxy]-piperidine-1-carboxylic acid tert-butyl ester (0.42 g, 14%).

Workup

  1. temperatureat reflux overnight
  2. concentrationIsopropanol was concentrated at reduced pressure
  3. custompartitioned between saturated aqueous sodium bicarbonate solution and methylene chloride
  4. extractionThe aqueous layer was extracted twice with methylene chloride
  5. washthe combined organics was washed with brine
  6. dry with materialdried (Na2SO4)
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customto provide a crude material
  10. customThe crude material was purified by ISCO (80 g silica gel column) chromatography

Sources & evidence

ORD record
ord-0d095ee6f3964383b787ab1705d1e0bb
Source dataset
uspto-grants-2013_11
Patent number
US08586588B2

Reaction notes

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