Potassium Carbonate → 1'-(1-(2-Iodobenzyl)-4-hydroxypiperidin-3-yl)-3,4-dihydrospiro[naphthalene-1(2H),4'-piperidine]

Participants

Reaction Steps

A mixture of the dihydrochloride of 21c (250 mg, 0.67 mmol), DMF (10 mL), potassium carbonate (463 mg, 3.35 mmol) and 2-iodobenzyl chloride (1.00 mmol, 254 mg) was stirred at room temperature for 18 h. Water (25 mL) and dichloromethane (2×25 mL) were added and the organic layer was extracted, washed with brine (25 mL), dried (Na2SO4) and concentrated. The crude product was purified by chromatography (silica gel, hexanes/ethyl acetate, 50/50) to afford 13c as a yellow oil. The latter was converted to the corresponding hydrochloride in satd HCl/ether and recrystallized twice from 50% i-PrOH-hexanes to yield 0.20 g (33%) of 13c; mp 258.8° C. 1H NMR (CDCl3)δ1.50-2.21 (2 m, 8, 2 N-CH2 --CH2), 2.45-2.57 (m, 2H, Ar-CH2CH2, J=10.2 Hz), 2.60- 2.76 (m, 2, CH2CHOH), 2.84 (m, 4, Ar-CH2 --CH2 --CH2), 2.88-3.00 (t, 2, CH2 --CH2CHOH, J=11.2 Hz), 3.09-3.13 (d, 2, N-CH2 --CHN, J=8.7 Hz), 3.50-3.64 (m, 3, Ar-CH2N+CH-N), 3.85 (s, 1, CHOH), 4.67 (s, 1, OH), 6.96-7.49 (m, 8 H, arom.), 7.83-7.87 (d, 1 H, arom., J=6.8 Hz).

Provenance & Evidence