Methyl iodide → HCID 67326281, compound

HRID 1397345Notes

Reaction equation

HRID 1397345 reaction equation
[H-].[Na+].[F:3][C:4]1[CH:9]=[CH:8][C:7]([C:10]2[O:11][CH:12]=[C:13]([CH2:15][C:16]#[N:17])[N:14]=2)=[CH:6][CH:5]=1.[CH3:18]I>C1COCC1>[F:3][C:4]1[CH:5]=[CH:6][C:7]([C:10]2[O:11][CH:12]=[C:13]([CH:15]([CH3:18])[C:16]#[N:17])[N:14]=2)=[CH:8][CH:9]=1

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 17541239HCID 17541239, compound

Product 1

HCID 67326281HCID 67326281, compoundYield 23%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

NaH (360 mg, 60% dispersion in oil) was added portionwise over 5 min to a solution of 2-(2-(4-fluorophenyl)oxazol-4-yl)acetonitrile (1.5 g, 7.42 mmol) in dry THF (60 mL) at 0° C. The resulting reaction mixture was slowly allowed to warm up to room temperature and stirred for 1 h. The reaction mixture was again cooled to 0° C. and a solution of methyl iodide (0.5 mL, 7.4 mmol) in dry THF (10 mL) was added dropwise at 0° C. over 30 min. The reaction mixture was stirred at 0° C. for 1 h and then at room temperature for another 1 h. The reaction mixture was quenched with saturated NH4Cl solution, diluted with EtOAc and further extracted with EtOAc. The combined extracts were washed with H2O and brine, dried over anhydrous Na2SO4, and concentrated under reduced pressure. The crude product was purified by column chromatography (silica 60-120 mesh, eluant 10% EtOAc in petroleum ether) to get 2-(2-(4-fluorophenyl)oxazol-4-yl)propanenitrile (360 mg, yield 23%). 1H NMR (400 MHz, CDCl3) δ 8.05-8.02 (m, 2H), 7.71-7.70 (d, J=1.1 Hz, 1H), 7.19-7.14 (t, J=8.7 Hz, 2H), 3.97-3.92 (m, 1H), 1.73-1.72 (d, J=7.2 Hz, 3H). MS (ESI) m/z: Calculated for C12H19FN2O: 216.07. found: 216.9 (M+H)+.

Workup

  1. customThe resulting reaction mixture
  2. temperatureThe reaction mixture was again cooled to 0° C.
  3. stirringThe reaction mixture was stirred at 0° C. for 1 h
  4. waitat room temperature for another 1 h
  5. customThe reaction mixture was quenched with saturated NH4Cl solution
  6. additiondiluted with EtOAc
  7. extractionfurther extracted with EtOAc
  8. washThe combined extracts were washed with H2O and brine
  9. dry with materialdried over anhydrous Na2SO4
  10. concentrationconcentrated under reduced pressure
  11. customThe crude product was purified by column chromatography (silica 60-120 mesh, eluant 10% EtOAc in petroleum ether)

Sources & evidence

ORD record
ord-84fc9b65de4f47469fed43ca955a3855
Source dataset
uspto-grants-2014_12
Patent number
US08901156B2

Reaction notes

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