Methanol → 6-(4-chlorophenyl)-7-methoxy-1-methyl-4H-isoxazolo[5,4-c]pyrido[4,3-e]azepine
Reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:14]3[C:15](F)=[N:16][CH:17]=[CH:18][C:13]=3[C:12]3[C:20]([CH3:23])=[N:21][O:22][C:11]=3[CH2:10][N:9]=2)=[CH:4][CH:3]=1.[H-].[Na+].[CH3:26][OH:27]>>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:14]3[C:15]([O:27][CH3:26])=[N:16][CH:17]=[CH:18][C:13]=3[C:12]3[C:20]([CH3:23])=[N:21][O:22][C:11]=3[CH2:10][N:9]=2)=[CH:4][CH:3]=1Participants
Procedure
To a solution of 6-(4-chlorophenyl)-7-fluoro-1-methyl-4H-isoxazolo[4,5-e]pyrido[3,4-c]azepine (0.030 g, 0.092 mmol) in MeOH (2 mL) was added sodium hydride (60% dispersed in mineral oil) (0.037 g, 0.915 mmol) at room temperature. The reaction was stirred at room temperature for 15 min (or until the gas evolution stopped) before it was heated to 80° C. for 75 min in a sealed vial. The reaction was then concentrated to dryness under vacuum, and the residue was purified by flash chromatography (hexane/EtOAc 19:1 to 5:5) to give 6-(4-chlorophenyl)-7-methoxy-1-methyl-4H-isoxazolo[5,4-c]pyrido[4,3-e]azepine as a white solid (0.031 g). 1H NMR (400 MHz, DMSO-d6) δ 8.42 (d, J=5.49 Hz, 1H), 7.43 (d, J=5.26 Hz, 1H), 7.39 (td, J=2.10, 8.70 Hz, 2H), 7.26 (td, J=2.10, 8.47 Hz, 2H), 5.24 (d, J=13.28 Hz, 1H), 4.11 (d, J=13.50 Hz, 1H), 3.61 (s, 3H), 2.55 (s, 3H); LC/MS m/z 340 [M+H]+.
Workup
- temperaturewas heated to 80° C. for 75 min in a sealed vial
- concentrationThe reaction was then concentrated to dryness under vacuum
- customthe residue was purified by flash chromatography (hexane/EtOAc 19:1 to 5:5)
Sources & evidence
- ORD record
- ord-1538b7803fc645b39742972390e2e33a
- Source dataset
- uspto-grants-2014_08
- Patent number
- US08796261B2
Reaction notes
Loading…