Potassium Cyanide → 3-(2-(4-Fluorophenyl)oxazol-4-yl)-3-hydroxypropanenitrile

HRID 1397421Notes

Reaction equation

[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[O:9][CH:10]=[C:11]([C:13](=[O:15])[CH3:14])[N:12]=2)=[CH:4][CH:3]=1.OP([O-])(O)=O.[K+].[C-:22]#[N:23].[K+]>CN(C=O)C.O.O>[F:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2[O:9][CH:10]=[C:11]([CH:13]([OH:15])[CH2:14][C:22]#[N:23])[N:12]=2)=[CH:6][CH:7]=1

Participants

Conditions

Temperature: 80 °C

Procedure

A solution of 1-(2-(4-fluorophenyl)oxazol-4-yl)ethanone (250 mg, 1.22 mmol) in DMF-H2O (7 mL; 2:5 v/v) was cooled to 0° C. and KH2PO4 (327 mg, 2.4 mmol) was added, followed by KCN (116 mg, 1.8 mmol). The reaction mixture was stirred at 80° C. 10 h and then diluted with water. The organic product was extracted with EtOAc and 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 8-12% EtOAc in petroleum ether) to afford 3-(2-(4-fluorophenyl)oxazol-4-yl)-3-hydroxypropanenitrile (60 mg, yield 21%) as a light yellow solid. 1H NMR (300 MHz, DMSO-d6) δ 8.11 (d, J=0.7 Hz, 1H), 8.03-7.98 (dd, J=8.9 Hz, 5.4 Hz, 2H), 7.40-7.34 (t J=8.9 Hz, 2H), 6.13-6.12 (d, J=5.3 Hz, 1H), 4.93-4.87 (m, 1H), 2.98-2.93 (dd, J=8.9 Hz, 5.8 Hz, 2H). MS (ESI) m/z: Calculated for C12H9FN2O2: 232.06. found: 233.0 (M+H)+.

Workup

extractionThe organic product was extracted with EtOAc
washthe combined extracts were washed with H2O and brine
dry with materialdried over anhydrous sodium sulfate
concentrationconcentrated under reduced pressure
customThe crude product was purified by column chromatography (silica gel 60-120 mesh, eluent 8-12% EtOAc in petroleum ether)

Sources & evidence

ORD record: ord-d4851385e00f4b9d9b8d09929d6d6ad8
Source dataset: uspto-grants-2014_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08901156B2

Reaction notes

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