1,4-Dioxane hydrochloride → 1-tert-butylcarbonylmethyl-2-oxo-3-amino-5-cyclohexyl-8-methyl-1,3,4,5-tetrahydro-2H-1,5-benzodiazepine

HRID 1979440Notes

Reaction equation

Cl.O1CCOCC1.[C:8]([C:12]([CH2:14][N:15]1[C:21]2[CH:22]=[C:23]([CH3:26])[CH:24]=[CH:25][C:20]=2[N:19]([CH:27]2[CH2:32][CH2:31][CH2:30][CH2:29][CH2:28]2)[CH2:18][CH:17]([NH:33]C(OC(C)(C)C)=O)[C:16]1=[O:41])=[O:13])([CH3:11])([CH3:10])[CH3:9]>C(O)C>[C:8]([C:12]([CH2:14][N:15]1[C:21]2[CH:22]=[C:23]([CH3:26])[CH:24]=[CH:25][C:20]=2[N:19]([CH:27]2[CH2:32][CH2:31][CH2:30][CH2:29][CH2:28]2)[CH2:18][CH:17]([NH2:33])[C:16]1=[O:41])=[O:13])([CH3:11])([CH3:9])[CH3:10]

Participants

Conditions

Temperature: 50 °C

Procedure

4N HCl-dioxane (7 ml) was added to a solution of 1-tert-butylcarbonylmethyl-2-oxo-3-tert-butoxycarbonylamino-5-cyclohexyl-8-methyl-1,3,4,5-tetrahydro-2H-1,5-benzodiazepine (517 mg) in ethanol (20 ml), the mixture was stirred at 50° C. for one hour. The reaction mixture was concentrated under reduced pressure, neutralized with saturated aqueous sodium bicarbonate, and extracted with methylene chloride. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and purified by silica gel column chromatography(chloroform:methanol=20:1), to thereby obtain 400 mg of the title compound (Yield: 98%).

Workup

concentrationThe reaction mixture was concentrated under reduced pressure
extractionextracted with methylene chloride
washThe organic layer was washed with saturated brine
dry with materialdried over anhydrous sodium sulfate
custompurified by silica gel column chromatography(chloroform:methanol=20:1)

Sources & evidence

ORD record: ord-f030cc8eee5747b89467b4a49df1e0ae
Source dataset: uspto-grants-2001_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06239131B1

Reaction notes

Loading…