2-Methoxybenzaldehyde → (+/-)-n-Isobutyl-4-(2-methoxybenzyl)-n-(2,3,4,5-tetrahydro-1-benzoxepin-8-ylmethyl)morpholine-2-carboxamide hydrochloride

Participants

Reaction Steps

A mixture of 31 mg (0.080 mmol) of (±)-N-isobutyl-N-(2,3,4,5-tetrahydro-1-benzoxepin-8-ylmethyl)morpholine-2-carboxamide hydrochloride, 0.0106 mL (0.088 mmol) of o-anisaldehyde, and 6.6 mg (0.080 mmol) of sodium acetate in 0.5 mL of 1,2-dichloroethane was stirred under nitrogen at ambient temperature for 10 minutes and 19 mg (0.088 mmol) of sodium triacetoxyborohydride was added. The mixture was stirred overnight then diluted with 5 mL of ethyl acetate and washed with 2 mL each of saturated sodium bicarbonate solution, water and brine, dried over sodium sulfate, filtered, and concentrated under reduced pressure to give 41 mg of a colorless gum. Preparative TLC (60% ethyl acetate/hexanes) gave 25 mg (68%) of product free-base as a gum. The gum was taken up in 1 mL of methanol, treated with 5 drops of 4M HCl in dioxane, and the mixture was concentrated. The residue was triturated with ether, and dried under vacuum to give the hydrochloride salt as a solid white foam. MS (m+1)=467.3; H NMR (400 MHz, CD3OD) 7.45 (m, 2H), 7.10 (m, 3H), 6.85 (m, 2H), 4.97 (m, 1H), 4.81 (m, 1H), 4.56-4.39 (m, 3H), 4.1-3.7 (m, 8H), 3.6-3.2 (m, 3H), 3.2-2.85 (m, 2H), 2.77 (d, 2H, J 6 Hz), 2.04 (m, 1H), 1.94 (m, 2H), 1.70 (m, 2H), 0.90 (m, 6H).

Provenance & Evidence