7-Chloro-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione → 7-Chloro-2,3,4,5-tetrahydro-1H-1,4-benzodiazepine

Temperature

63 °C

7-chloro-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione (15.05 g, 71.4 mmol) was stirred in THF (120 mL). Lithium aluminum hydride (1M solution in THF, 214.5 mL, 214.4 mmol) was added gradually. When the addition was completed, the reaction mixture was heated to 63° C. and held for 19 hours. After 19 hours, the reaction was cooled to room temperature, and then to 0° C. The reaction mixture was quenched with water, 15% NaOH and another portion of water. After letting the reaction mixture stir for one hour, the precipitate was filtered off and washed with ethyl acetate. THF was removed, and the contents of the reaction flask were transferred to a separatory funnel with ethyl acetate and water. The contents in the separatory funnel were then extracted with ethyl acetate (3×). The combined organic extracts were washed with brine (2×), then dried with magnesium sulfate, filtered and concentrated to give the crude desired product. Further purification by recrystallization (methylene chloride) yielded orange crystals.

1. additionWhen the addition
2. waitAfter 19 hours
3. temperaturethe reaction was cooled to room temperature
4. customto 0° C
5. customThe reaction mixture was quenched with water, 15% NaOH
6. filtrationthe precipitate was filtered off
7. washwashed with ethyl acetate
8. customTHF was removed
9. customthe contents of the reaction flask were transferred to a separatory funnel with ethyl acetate and water
10. extractionThe contents in the separatory funnel were then extracted with ethyl acetate (3×)
11. washThe combined organic extracts were washed with brine (2×)
12. dry with materialdried with magnesium sulfate
13. filtrationfiltered
14. concentrationconcentrated

ORD record

ord-5a8b9bf66d624aaca03f4fd021a2d8b9

Source dataset

uspto-grants-2010_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07687620B2