Acetonitrile → 3-(3-Fluoro-4-methylphenyl)-1,2,4-oxadiazole
Reaction equation
[F:1][C:2]1[CH:3]=[C:4]([CH:9]=[CH:10][C:11]=1[CH3:12])[C:5](=[N:7][OH:8])[NH2:6].[CH:13](OCC)(OCC)OCC.C(#N)C>FC(F)(F)C(O)=O.O>[F:1][C:2]1[CH:3]=[C:4]([C:5]2[N:6]=[CH:13][O:8][N:7]=2)[CH:9]=[CH:10][C:11]=1[CH3:12]Participants
Conditions
- Temperature
- 45 °C
Procedure
A suitable vessel equipped with a mechanical stirrer under a N2 atmosphere was charged with 3-fluoro-N′-hydroxy-4-methylbenzimidamide (302.52 g, 1.79 mol), triethyl orthoformate (382.5 mL, 341.1 g, 2.3 mol) and acetonitrile (1512 mL). The reaction mixture was heated to 45° C. and trifluoroacetic acid (6.72 mL, 10.08 g, 87.6 mmol) was added at this temperature. The reaction mixture was heated at 60° C. for an additional 90 minutes, then cooled to room temperature. Water (3 L) was added dropwise over a period of 60 minutes. The slurry was cooled to 4° C. and stirred at this temperature for 30 minutes. The solid was filtered and dried in vacuum at 50° C. for 12 hours to give 3-(3-fluoro-4-methylphenyl)-1,2,4-oxadiazole as a white solid (306 g, 95.6%). HPLC indicated 99.8% chemical purity. 1H-NMR (CDCl3, 400 MHz) δ8.67 (s, 1H), 7.71 (m, 2H), 7.23 (t, J=8 HZ, 1H), 2.28 (s, 3H); 13C-NMR (CDCl3, 400 MHz) δ166.9447, 164.7258, 162.5473, 160.1066, 132.0480, 132.0077, 128.5987, 122.9910, 122.9507, 114.2568, 114.0147, 14.6902. 19F-NMR (CDCl3, 400 MHz) δ−115.94, −115.96.
Workup
- customA suitable vessel equipped with a mechanical stirrer under a N2 atmosphere
- temperatureThe reaction mixture was heated at 60° C. for an additional 90 minutes
- temperaturecooled to room temperature
- temperatureThe slurry was cooled to 4° C.
- filtrationThe solid was filtered
- customdried in vacuum at 50° C. for 12 hours
Sources & evidence
- ORD record
- ord-b7324fae93bc48dd8cec3eb5723750d7
- Source dataset
- uspto-grants-2011_12
- Patent number
- US08084477B2
Reaction notes
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