Water → 4-Benzyl-7-methoxy-1,3,4,5-tetrahydro-benzo[e][1,4]diazepin-2-one

HRID 1041594Notes

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]=1

Participants

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-ea0b874834e647f882f89daaf046f4de
Source dataset: uspto-grants-2013_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08552186B2

Reaction notes

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