Sulfuric Acid → Cetirizine

Participants

Reaction Steps

To a stirred suspension of hydroxyzine dihydrochloride (70.0 g, 0.156 mol) in acetone (560 ml), Jones reagent (130 ml, 0.351 mol), which was made by adding sulphuric acid (115 ml) to a solution of chromium trioxide (133.7 g) in water (250 ml) and adding water to the total volume of 500 ml, was added dropwise in a period of 2 hours. The stirring was continued for further 17 hours at room temperature. Isopropanol (10 ml) was added dropwise and the mixture was stirred for 1 hour. 25% aqueous NaOH solution (250 ml) was added slowly to adjust pH to ca. 12. Celite (100 g) was then added and the suspension was stirred for 20 min. The mixture was filtered through a pad of celite (13×2 cm) and washed with 2:1 acetone-water (3×200 ml). Evaporation of the most acetone from the combined filtrate gave a aqueous suspension. The suspension was washed by ethyl acetate (100 ml) and 5% aqueous NaCl solution (100 ml) This washing procedure was repeated 5 times. Water (500 ml) was added to the isolated middle oily layer. 5% HCl aqueous solution was used to adjust pH to ca 2. After being washed with dichloromethane (2×200 ml), the aqueous solution was adjusted to pH=6 with 25% NaOH solution and extracted with dichloromethane (3×250 ml). The combined organic extract was treated with charcoal (10 g) and filtered through a pad of celite (13×2 cm). Evaporation of solvent afforded the titled compound as a pale white foam (36.8 g, yield 60%) δH (CDCl3 ; 300 MHz) 13.73 (1H, br), 7, 14-7.36 (9H, m), 4.24 (1H, s), 3.95 (2H, s), 3.68-3.78 (2H, m), 3.09 (4H, br), 2.89-2.98 (2H, m), 2.62 (4H, br); δC (CDCl3 ; 75.47 MHz) 175.09, 141.33, 140.53, 132.93, 128.95, 128.89, 128.83, 127.56, 74.65, 70.23, 66.56, 56.72, 53.09, 49.24; Found: M+, 388.1544. C21H25Cl1N2O3 requires M, 388.1554.

Provenance & Evidence