Sodium hydride → HCID 72231365, compound

HRID 1505826Notes

Reaction equation

HRID 1505826 reaction equation
[CH:1]1([OH:4])[CH2:3][CH2:2]1.[H-].[Na+].F[C:8]1[CH:15]=[C:14]([F:16])[CH:13]=[CH:12][C:9]=1[C:10]#[N:11]>O1CCOCC1.C(OCC)(=O)C>[CH:1]1([O:4][C:8]2[CH:15]=[C:14]([F:16])[CH:13]=[CH:12][C:9]=2[C:10]#[N:11])[CH2:3][CH2:2]1

Participants

6

Reactant 3

HCID 24758Sodium hydrideHCID 775452,4-DifluorobenzonitrileHCID 123361Cyclopropanol

Product 1

HCID 72231365HCID 72231365, compound

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent2×

Procedure

A solution cyclopropanol (1.9 g, 29 mmol) in 20 mL dioxane was added dropwise to a 0° C. solution of Sodium hydride (60% dispersion in mineral oil, 1.04 g, 26 mmol) in 80 mL dioxane. The reaction mixture was allowed to warm to room temperature, 2,4-difluorobenzonitrile (3.48 g, 25 mmol) was added portionwise, and reaction temperature raised to 95° C. The reaction solution was cooled to room temperature after stirring for 18 hours, diluted with ethyl acetate, washed twice with water and twice with brine, dried over MgSO4, filtered, and concentrated onto silica gel. Purification by silica gel chromatography (0-10% EtOAc/hexanes) afforded 2-cyclopropoxy-4-fluorobenzonitrile. 1H-NMR (400 MHz, Chloroform-d) δ 7.52 (dd, J=8.6, 6.2 Hz, 1H), 7.05 (dd, J=10.5, 2.3 Hz, 1H), 6.73 (td, J=8.2, 2.3 Hz, 1H), 3.87-3.76 (m, 1H), 0.87 (m, 4H).

Workup

  1. customreaction temperature
  2. temperatureraised to 95° C
  3. temperatureThe reaction solution was cooled to room temperature
  4. washwashed twice with water and twice with brine
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated onto silica gel
  8. customPurification by silica gel chromatography (0-10% EtOAc/hexanes)

Sources & evidence

ORD record
ord-a8f4862a81ef4e7dbbfab9e6c9207605
Source dataset
uspto-grants-2015_12
Patent number
US09216996B2

Reaction notes

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