Boron trifluoride etherate → 2-(2-(4-Fluorophenyl)oxazol-4-yl)-2-methoxyacetonitrile

HRID 1397435Notes

Reaction equation

HRID 1397435 reaction equation
C[Si]([C:5]#[N:6])(C)C.[CH3:7][O:8][CH:9](OC)[C:10]1[N:11]=[C:12]([C:15]2[CH:20]=[CH:19][C:18]([F:21])=[CH:17][CH:16]=2)[O:13][CH:14]=1.B(F)(F)F.CCOCC>>[F:21][C:18]1[CH:17]=[CH:16][C:15]([C:12]2[O:13][CH:14]=[C:10]([CH:9]([O:8][CH3:7])[C:5]#[N:6])[N:11]=2)=[CH:20][CH:19]=1

Participants

4

Reactant 3

HCID 8000Boron trifluoride etherateHCID 82115Trimethylsilyl cyanideHCID 673246204-(Dimethoxymethyl)-2-(4-fluorophenyl)oxazole

Product 1

HCID 673263782-(2-(4-Fluorophenyl)oxazol-4-yl)-2-methoxyacetonitrileYield 25.5%

Procedure

Trimethylsilyl cyanide (4.13 g, 41.76 mmol) was added to a solution of 4-(dimethoxymethyl)-2-(4-fluorophenyl)oxazole (400 mg, 1.69 mmol) at room temperature, followed by boron trifluoride diethyl etherate (37 mg, 0.26 mmol). The reaction mixture was stirred for 20 min, quenched with saturated aqueous NaHCO3 solution, and extracted with EtOAc. The combined extracts were washed with H2O and brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The crude product was purified by column chromatography (silica gel 60-120 mesh, eluent 8-10% EtOAc in petroleum ether) to afford 2-(2-(4-fluorophenyl)oxazol-4-yl)-2-methoxyacetonitrile (100 mg, yield 16%) as a light yellow liquid. 1H NMR (400 MHz, CDCl3) δ 8.08-8.06 (m, 2H), 7.90 (d, J=0.9 Hz, 1H), 7.19-7.15 (m, 2H), 5.29 (d, J=0.9 Hz, 1H), 3.62 (s, 3H). MS (ESI) m/z: Calculated for C12H9FN2O2: 232.21. found: 232.9 (M+H)+.

Workup

  1. customquenched with saturated aqueous NaHCO3 solution
  2. extractionextracted with EtOAc
  3. washThe combined extracts were washed with H2O and brine
  4. dry with materialdried over anhydrous sodium sulfate
  5. concentrationconcentrated under reduced pressure
  6. customThe crude product was purified by column chromatography (silica gel 60-120 mesh, eluent 8-10% EtOAc in petroleum ether)

Sources & evidence

ORD record
ord-3f4bb85799c34d22aa354eba5e8f21c5
Source dataset
uspto-grants-2014_12
Patent number
US08901156B2

Reaction notes

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