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

Temperatur

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 (1 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 ethanol/ethyl 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 ethanol/ethyl acetate)

ORD-Eintrag

ord-0c1a0594e0f848c28e5fc146d8bc5f87

Quelldatensatz

uspto-grants-2010_03

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US07687620B2