Hydrazine hydrate (1:1) → HCID 72207820, compound

HRID 475069Notes

Reaction equation

HRID 475069 reaction equation
[F:1][C:2]1([F:11])[CH2:5][CH:4]([C:6](=O)[CH2:7][C:8]#[N:9])[CH2:3]1.O.[NH2:13][NH2:14]>CCO>[F:1][C:2]1([F:11])[CH2:5][CH:4]([C:6]2[NH:14][N:13]=[C:8]([NH2:9])[CH:7]=2)[CH2:3]1

Participants

4

Reactant 2

HCID 24654Hydrazine hydrate (1:1)HCID 72207271Cyclobutanepropanenitrile, 3,3-difluoro-β-oxo-

Product 1

HCID 72207820HCID 72207820, compoundYield 39%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
75 °C

Procedure

To a solution of 3-(3,3-difluorocyclobutyl)-3-oxopropanenitrile (12.5 g, 78.6 mmol) in EtOH (250 mL) was added hydrazine hydrate (5.9 g, 117.9 mmol) and the resulting mixture was stirred at 75° C. overnight. After concentrating the reaction mixture in vacuo, the residue was redissolved in EtOAc (500 mL) and washed with satd. aq. NaHCO3. The aqueous layer was extracted with EtOAc and the combined extracts washed with brine (100 mL), dried (Na2SO4), filtered and concentrated in vacuo. The crude product was purified by SiO2 chromatography eluting with DCM/MeOH (10:1) to afford 3.46 g (39%) of 85 as a light yellow solid: 1H NMR (400 MHz, DMSO-d6) δ 11.20 (br s, 1H), 5.23 (s, 1H), 4.65 (br s, 2H), 3.16-3.13 (m, 1H), 2.88-2.84 (m, 2H), 2.64-2.57 (m, 2H); MS (ESI+) m/z=174 [M+1]+.

Workup

  1. concentrationAfter concentrating the reaction mixture in vacuo
  2. dissolutionthe residue was redissolved in EtOAc (500 mL)
  3. washwashed with satd
  4. extractionThe aqueous layer was extracted with EtOAc
  5. washthe combined extracts washed with brine (100 mL)
  6. dry with materialdried (Na2SO4)
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customThe crude product was purified by SiO2 chromatography
  10. washeluting with DCM/MeOH (10:1)

Sources & evidence

ORD record
ord-70833144b7cd4e9db1e14122a80334b9
Source dataset
uspto-grants-2014_01
Patent number
US08637537B2

Reaction notes

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