Barium hydroxide → HCID 19705016, compound

Participants

Reaction Steps

4-(4-Chlorophenyl)-2-ethyl-9-methyl-6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepine (10 g) is dissolved in diethyl carbonate (150 ml) in a nitrogen stream, and 60% sodium hydride (2.0 g) is added with stirring at room temperature. The mixture is refluxed under heating for 2 hours and cooled to 50° C. with ice water. Ethyl bromovalerate (7.9 ml) is added. After stirring at 100° C. for 2 hours, the reaction mixture is poured on ice water (1 l) and extracted with ethyl acetate. The organic layer is washed with saturated brine, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue is purified by silica gel column chromatography (ethyl acetate:methanol=100:l) and crystallized from isopropyl ether and ethyl acetate to give 8.3 g of (±)-ethyl 5-(4-(4-chlorophenyl)-6-ethoxycarbonyl-2-ethyl-9-methyl-6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepin-6-yl) valerate as white powdery crystals. (±)-Ethyl 5-(4-(4-chlorophenyl)-6-ethoxycarbonyl-2-ethyl-9-methyl-6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepin-6-yl)valerate (8.2 g) is dissolved in a mixture of ethanol (90 ml) and water (30 ml), and barium hydroxide 8 hydrate (19 g) is added. The mixture is refluxed under heating for 4 hours. After the completion of the reaction, ethanol is distilled away under reduced pressure and adjusted to pH 1 with 6N hydrochloric acid. The mixture is stirred for 30 minutes and adjusted to pH 4 with a saturated aqueous solution of sodium hydrogencarbonate and extracted with chloroform. The organic layer is washed with a saturated brine, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue is crystallized from ethyl acetate and isopropyl ether and recrystallized from chloroform and methanol to give 3.2 g of (±)-5-(4-(4-chlorophenyl)-2-ethyl-9-methyl-6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepin-6-yl)valeric acid as white powdery crystals, melting point 257°-260° C.

Provenance & Evidence