Citric Acid → HCID 69050218, compound

Participants

Reaction Steps

A solution of 3-(4-fluoro-phenyl)-2-isopropyl-2,4,5,6,7,8-hexahydro-1,2,6-triaza-azulene (160.0 g, 0.585 mol) in methanol (1.2 L) was treated with a solution of citric acid (123.7 g, 0.644 mol) in methanol (500 mL). The solution was stirred for 18 h at rt, then was diluted with EtOAc (1 L) and stirred another 24 h. The resulting precipitate was filtered, washed with 4:1 EtOAc/methanol, and dried to give a first crop of the title compound. The filtrate was concentrated and basified to pH 13-14 with 3 N KOH. The aqueous solution was extracted with EtOAc (3×200 mL). The combined organic layers were dried (Na2SO4) and concentrated to recover 52 g of the free base of the title compound. The free base was diluted with methanol (300 mL) and treated with citric acid (21.5 g, 0.112 mol). The mixture was stirred for 18 h, concentrated to approx. 150 mL, diluted with EtOAc (300 mL), and stirred for 24 h. The resulting precipitate was collected by filtration, washed with 4:1 EtOAc/methanol, and dried, to give a second crop of the title compound. mp 164-166° C. 1H NMR (400 MHz, D2O): 7.26-7.23 (m, 2H), 7.18-7.14 (t, J=8.9, 2H), 4.29-4.24 (m, 1H), 3.31-3.29 (t, J=5.3, 2H), 3.18-3.16 (t, J=5.3, 2H), 3.03-3.01 (t, J=5.6, 2H), 2.75 (d, J=15.5, 2H), 2.64 (d, J=15.5, 2H), 2.65-2.63 (m, 2H), 1.21 (d, J=6.7, 6H). Anal. calcd. for C22H28FN3O7: C, 56.77; H, 6.06; N, 9.03. Found: C, 56.59; H, 6.42; N, 9.04.

Provenance & Evidence