N-(2-(benzyloxy)phenyl)-3-fluoroisonicotinamide → 3-fluoro-N-(2-hydroxyphenyl)isonicotinamide
Reaction equation
C([O:8][C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=1[NH:15][C:16](=[O:24])[C:17]1[CH:22]=[CH:21][N:20]=[CH:19][C:18]=1[F:23])C1C=CC=CC=1>Br.C(O)(=O)C.O.C(=O)(O)[O-].[Na+]>[F:23][C:18]1[CH:19]=[N:20][CH:21]=[CH:22][C:17]=1[C:16]([NH:15][C:10]1[CH:11]=[CH:12][CH:13]=[CH:14][C:9]=1[OH:8])=[O:24]Participants
Procedure
Title compound 445 (1.99 g, 6.18 mmol) was dissolved in the solution of HBr (33% in AcOH, 15.0 mL) and acetic acid (10.0 mL). The reaction mixture was stirred at room temperature for 4 hours. The mixture was diluted with water and basified with solid sodium bicarbonate until alkaline. More water was added to dissolve the salt and the aqueous layer was extracted with ethyl acetate (twice). The combined organic layers were washed with water and brine, dried over sodium sulfate, filtered and evaporated. The residue was triturated in 30% ethyl acetate in hexanes to afford title compound 446 (1.21 g, 84%) as a beige-yellow solid. 1H NMR (DMSO-d6) δ (ppm): 10.02 (s, 1H), 9.75 (s, 1H), 8.75 (d, J=2.0 Hz, 1H), 8.59 (dd, J=4.8, 1.3 Hz, 1H), 7.94 (dd, J=8.0, 1.6 Hz, 1H), 7.76 (dd, J=6.1, 4.9 Hz, 1H), 7.03 (ddd, J=8.0, 7.4, 1.6 Hz, 1H), 6.92 (dd, J=8.0, 1.4 Hz, 1H), 6.84 (td, J=7.6, 1.3 Hz, 1H). MS (m/z): 233.2 (M+H).
Workup
- dissolutionto dissolve the salt
- extractionthe aqueous layer was extracted with ethyl acetate (twice)
- washThe combined organic layers were washed with water and brine
- dry with materialdried over sodium sulfate
- filtrationfiltered
- customevaporated
- customThe residue was triturated in 30% ethyl acetate in hexanes
Sources & evidence
- ORD record
- ord-1cc0e0cec25645f0a2bc5bfa92671787
- Source dataset
- uspto-grants-2015_11
- Patent number
- US09193749B2
Reaction notes
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