1,2-Dibromoethane → HCID 14459740, compound

1,2-Dibromoethane (0.5 ml) was added to a refluxing slurry of magnesium chips (12 gm) in tetrahydrofuran (60 ml) to initiate a Grignard reaction. N-Methyl-4-chloropiperidine (55 ml) in tetrahydrofuran (100 ml) was added rapidly. The mixture was refluxed for 1 hour, during which a white precipitate formed. A solution of 9-bromo-1,2-dihydrobenzo[b]pyrrolo[3,2,1-jk][1,4]benzodiazepine (30 gm) in tetrahydrofuran (150 ml) was added at 0° C. After one hour of stirring, the mixture was poured into cold saturated ammonium chloride solution (750 ml) and extracted with ethyl acetate (2×400 ml). The ammonium chloride solution was basified with ammonium hydroxide and extracted once with ethyl acetate (400 ml). The combined ethyl acetate solutions were washed with brine (2×500 ml), dried over anhydrous magnesium sulfate and concentrated to a solid (38 gm). The crude solid was purified by flash chromatography (700 gm silica, eluted with 4% methanol/dichloromethane, 6 L; 4 % methanol/0.5% ammonium hydroxide/dichloromethane, 4 L). The fractions containing the desired product were pooled and concentrated to give 23 gm of a solid. Recrystallization from dichloromethane/ethanol (200 ml:1 L) yielded 17.0 gm of crystals, m.p. 206°-208° C.

1. customa Grignard reaction
2. temperatureThe mixture was refluxed for 1 hour, during which a white precipitate
3. customformed
4. extractionextracted with ethyl acetate (2×400 ml)
5. extractionextracted once with ethyl acetate (400 ml)
6. washThe combined ethyl acetate solutions were washed with brine (2×500 ml)
7. dry with materialdried over anhydrous magnesium sulfate
8. concentrationconcentrated to a solid (38 gm)
9. customThe crude solid was purified by flash chromatography (700 gm silica, eluted with 4% methanol/dichloromethane, 6 L; 4 % methanol/0.5% ammonium hydroxide/dichloromethane, 4 L)
10. additionThe fractions containing the desired product
11. concentrationconcentrated

ORD record

ord-e619992847894ac7a9b55fcab688d7c4

Source dataset

uspto-grants-1989_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US04840947