4-(4,6-Dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride → 6-(1H-indol-3-yl)hexanoic acid (4-dimethylamino-4-phenylcyclohexylmethyl)amide

Participants

Reaction Steps

The non-polar diastereoisomer of (4-aminomethyl-1-phenylcyclohexyl)dimethylamine (232 mg, 1.0 mmol.) and 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride (415 mg, 1.5 mmol.) were added to a solution of 6-(1H-indol-3-yl)hexanoic acid (231 mg, 1.0 mmol.) in abs. methanol, and stirring was carried out for 24 h at RT. For working up, the mixture was concentrated and the residue was suspended in water (10 ml), adjusted to pH 11 with 5M NaOH and extracted with EE (4×10 ml). The combined organic extracts were washed with 1M NaOH (2×2 ml), dried, filtered and concentrated. The residue was purified by flash chromatography on silica gel (50 g) with methanol/EE (1:3, 440 ml) and the non-polar diastereoisomer of 6-(1H-indol-3-yl)hexanoic acid (4-dimethylamino-4-phenylcyclohexylmethyl)amide (266 mg) was isolated in the form of a crystalline solid. 265 mg (6 mmol.) thereof were dissolved in 2-butanone, and chlorotrimethylsilane (113 μl, 0.9 mmol.) was added thereto. A colourless, tacky precipitate immediately formed and was converted into a fine pale-pink solid by the addition of ether. The solid was filtered off, washed with cold ether (3×2 ml) and dried in vacuo. The hydrochloride of 6-(1H-indol-3-yl)hexanoic acid (4-dimethylamino-4-phenylcyclohexylmethyl)amide was thus obtained in a yield of 274 mg (pale-pink solid, m.p. 120–125° C.).

Provenance & Evidence