Tetrahydrothiophene → 5-Phenyl-1-(piperidin-4-yl)-1,3-dihydro-2H-1,4-benzodiazepin-2-one

Participants

Reaction Conditions

Reaction Steps

To a solution of 1 g (2.6 mmol) of 12 in 1.1 ml (2.6×5 mmol) of tetrahydrothiophene is added 2 ml of methanesulfonic acid, and the mixture is heated at 110° C. (bath temperature) for 50 minutes. The reaction mixture is poured into ice water and shaken with ether. The aqueous layer is besified with aqueous potassium carbonate and extracted with methylene chloride. The methylene chloride layer is concentrated, and the residue is dissolved in 1 ml of methanol and mixed with 0.27 ml of 48% hydrobromic acid. The resultant crystals are recrystallized from methylene chloride-methanol to give 881 mg of 13 as crystals melting at 281°-283° C. (dec.). The yield is 86%.

Provenance & Evidence