Sulfuric Acid → 5-Chloro-2-methyl-2,3,3a,12b-tetrahydrodibenzo(2,3:6,7)oxepino(4,5-c)pyrrole

Participants

Reaction Conditions

Reaction Steps

Concentrated sulfuric acid (618 mg, 6.3 mmol) is added carefully at −10° C. to a suspension of lithium aluminum hydride (478 mg, 12.6 mmol) in dry THF (20 mmol). Then a solution of (6) (1.0 g, 3.1 mmol) in THF (5 mL) is added dropwise and the mixture stirred at 40° C. for 6 hr. After quenching sequentially with H2O (0.5 mL), 15% NaOH (0.5 mL) and H2O (1.5 mL), the white precipitate is filtered and the filtrate evaporated. The residue is purified by flash chromatography (Heptane:Ethyl Acetate 7:3) giving 612 mg (69%) of trans-(5-Chloro-2-methyl-2,3,3a,12b-tetrahydro-1H-dibenz[2,3:6,7]oxepino-[4,5-c]pyrrole (Asenapine) as a slightly yellow oil.

Provenance & Evidence