Water → 4-Benzyl-7-methoxy-1,3,4,5-tetrahydro-benzo[e][1,4]diazepin-2-one
Reaction equation
[CH2:1]([N:8]1[CH2:17][C:16](=[O:18])[C:15]2[C:10](=[CH:11][C:12]([O:19][CH3:20])=[CH:13][CH:14]=2)[CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[N-:21]=[N+]=[N-].[Na+].O.[OH-].[Na+]>CS(O)(=O)=O>[CH2:1]([N:8]1[CH2:9][C:10]2[CH:11]=[C:12]([O:19][CH3:20])[CH:13]=[CH:14][C:15]=2[NH:21][C:16](=[O:18])[CH2:17]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1Participants
Conditions
- Temperature
- 65 °C
Procedure
To a solution of 2-benzyl-7-methoxy-2,3-dihydro-1H-isoquinolin-4-one (7.0 g, 26.2 mmol) in methanesulfonic acid (50 mL) was added sodium azide (3.4 g, 52.4 mmol) portionwise with stirring (Caution: mild exotherm, gas evolution). The mixture was heated to 65° C. for two hours before being cooled to ambient temperature. Water (100 mL) was added, the mixture was cooled in an ice-water bath, and the pH was adjusted to 7-8 (10N NaOH). The gummy precipitate was extracted (DCM), the organic phase was washed with brine, dried over magnesium sulfate, filtered and concentrated. Further purification by flash chromatography over silica gel (DCM/MeOH) gave 4-benzyl-7-methoxy-1,3,4,5-tetrahydro-benzo[e][1,4]diazepin-2-one (5.4 g, 73%) as a tan solid; 1H NMR (400 MHz, DMSO-d6) δ 9.80 (s, 1H), 7.33 (m, 5H), 6.97 (d, J=8 Hz, 1H), 6.87 (d, J=8 Hz, 1H), 6.82 (s, 1H), 3.73 (s, 3H), 3.67 (s, 4H), 3.09 (s, 2H); MS (m/e) 283 (M+1); mp 134° C.
Workup
- temperaturebefore being cooled to ambient temperature
- temperaturethe mixture was cooled in an ice-water bath
- extractionThe gummy precipitate was extracted (DCM)
- washthe organic phase was washed with brine
- dry with materialdried over magnesium sulfate
- filtrationfiltered
- concentrationconcentrated
- customFurther purification by flash chromatography over silica gel (DCM/MeOH)
Sources & evidence
- ORD record
- ord-08e62f45a1f94d408e64d4556da233e1
- Source dataset
- uspto-grants-2012_04
- Patent number
- US08148391B2
Reaction notes
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