3-Quinuclidinone → N-(4-Bromo-2-(2,2-dimethoxyethyl)phenyl)-quinuclidin-3-amine

Participants

Reaction Steps

Compound 67 (160 mg, 0.615 mmol) and quinuclidin-3-one (115.5 mg, 0923 mmol) were stirred in acetic acid (5 mL) under argon in the presence of anhydrous sodium sulfate (874 mg, 6.150 mmol) at room temperature for 30 minutes. Sodium triacetoxyborohydride (391 mg, 1.845 mmol) was then added and the mixture stirred for 24 hours at room temperature. Thin layer chromatography in a solvent system of 2M NH3 in methanol:CH2Cl2, 5:95 shows incomplete consumption of 67, thus a second portion of quinuclidin-3-one (38.4 mg, 0.307 mmol) is added and the mixture stirred for a further 20 hours. After dilution with a mixture of 8:1 ethyl acetate:hexanes, the reaction is quenched with saturated sodium bicarbonate. The mixture was transferred to a separatory funnel and the organic layer separated. The organic layer was dried over sodium sulfate and concentrated under reduced pressure and the residue purified via chromatography on silica gel (2M NH3 in methanol:CH2Cl2, 2.5:97.5 to 5:95) to yield a colorless residue, 68 (137 mg, 60.3%). 1H NMR (DMSO-d6) δ 1.25-1.39 (m, 1H), 1.53-1.80 (2×m, 3H), 1.86-1.94 (m, 1H), 2.64-2.77 (m, 4H), 2.80 (d, 2H, J=5.2 Hz), 3.14-3.24 (m, 1H), 3.27 and 3.29 (2×s, 6H), 3.34-3.40 (m, 1H), 4.54 (t, 1H, J=5.2 Hz), 5.04 (d, 1H, J=5.8 Hz), 6.43 (d, 1H, J=8.3 Hz), 7.13-7.15 (m, 1H), 7.17 (s, 1H); ESI-MS (m/z, %): 369/371 (MH+, 100%).

Provenance & Evidence