Hydrochloric Acid → HCID 9804381, compound

Participants

Reaction Steps

4-[2-Pyrrolidinoethoxy]phenyl bromide (1.41 g, 5.20 mmol) in dry THF (50 ml) was added to magnesium turnings (312 mg, 13.0 mmol) in a dry 3-necked round bottom flask under an oxygen-free nitrogen atmosphere and the mixture was maintained under gentle reflux. 1,2-Dibromoethane (0.22 ml, 2.60 mmol) was added dropwise over a period of 1/2 hour. The mixture was heated gently until the magnesium was nearly consumed (ca. 1/2 hour). 2-(p-Chlorobenzyl)-6-methoxy-3(2H)-benzofuranone (740 mg, 2.60 mmol) in THF (50 ml) was added dropwise to the mixture at 0°C. The reaction mixture was allowed to warm to room temperature and refluxed for 18 hours. The cooled mixture was quenched with saturated ammonium chloride (30 ml), extracted with dichloromethane (3×40 ml), washed with water, dried (anhydrous sodium sulphate) and the solvent evaporated off to yield an oil which was dehydrated with concentrated hydrochloric acid (2 ml) in ethanol (25 ml). The mixture was refluxed for 2 hours, whereupon ethanol was removed. It was then basified with 10% sodium hydroxide (20 ml) and extracted with dichloromethane (3×40 ml). The dichloromethane extract was washed with water (3×20 ml), dried (anhydrous sodium sulphate) and the solvent was evaporated off to give a solid which was chromatographed on silica gel. Elution with (dichloromethene:hexane:triethylamine=1:2:0.3), yielded a colourless solid which was recrystallised from methanol to give 2-(p-chlorobenzyl)-3-[p-(2-pyrrolidinoethoxy)phenyl]-6-methoxybenzo[b]furan (2), m.p. 75° C. Dry hydrogen chloride gas was bubbled through an ethereal solution of the free base for 10 minutes and cooled to 0°C. The hydrochloride salt which precipitated out was filtered off at the pump, rinsed with ether, and recrystallised from isopropanol to yield white crystals of the hydrochloride salt. Yield (22%); m.p. 223°-225° C.; 1H-NMR (CDCl3) δ 1.82 (m, 4H, N(CH2CH2)2), 2.65 (br s, 4H, N(CH2CH2)2), 2.93 (t, 2H, J6.0 Hz, OCH2CH2N), 3.84 (s, 3H, OCH3), 4.16 (distorted t, 4H,J 6.0 Hz, OCH2CH2N, CH2 at C-2), 6.80-7.47 (m, 11H, ArH); m/z (%) 463 (M+ -HCl, 28), 461 (M+ -HCl, 10), 364 (17), 98 (38), 84 (100). (Found: C, 67.37, H, 5.92, N, 2.56, Cl, 13.95. C28H28ClNO3.HCl required C, 67.47, H, 5.66, N, 2.81, Cl, 14.23).

Provenance & Evidence