Aluminium lithium hydride → 2,3,4,5-Tetrahydro-8-(trifluoromethyl)-1H-1,4-benzodiazepine

Temperature

68 °C

To a solution of 8-(trifluoromethyl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione (1.5 g, 6.1 mmol) in THF (11 mL) at room temperature was added lithium aluminum hydride in THF (28 mL, 28 mmol) over 10 minutes. Once the addition was completed, the reaction was heated to 68° C. After 24 hours, additional lithium aluminum hydride in THF was added (12.3 mmol) over five minutes. After 3 hours, the reaction mixture was cooled to 0° C., and then quenched with water, 15% NaOH, and an additional portion of water. After filtering off the gray precipitate and rinsing with ethyl acetate, the solvent was removed from the filtrate. The resulting solid was then redissolved in ethyl acetate and transferred to a separatory funnel and washed with water (3×), dried with magnesium sulfate, filtered and concentrated to give a yellow solid. Further purification (15% ammonia in 2M solution of ethanollethyl acetate) yielded 0.918 g of desired product (69%).

1. additionOnce the addition
2. waitAfter 3 hours
3. temperaturethe reaction mixture was cooled to 0° C.
4. customquenched with water, 15% NaOH
5. filtrationAfter filtering off the gray precipitate
6. washrinsing with ethyl acetate
7. customthe solvent was removed from the filtrate
8. dissolutionThe resulting solid was then redissolved in ethyl acetate
9. customtransferred to a separatory funnel
10. washwashed with water (3×)
11. dry with materialdried with magnesium sulfate
12. filtrationfiltered
13. concentrationconcentrated
14. customto give a yellow solid
15. customFurther purification (15% ammonia in 2M solution of ethanollethyl acetate)

ORD record

ord-c64e9d4bff124b489e4b53dc42624698

Source dataset

uspto-grants-2006_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07129237B2