Sodium hydride → HCID 66898649, compound

Participants

Reaction Conditions

Reaction Steps

To a stirred solution of (R)-(+)-3-aminoquinuclidine dihydrochloride (287 mg, 1.4 mmol) in 1,4-dioxane (10 mL) was added 60% sodium hydride (86 mg, 3.6 mmol) in portions. The mixture was heated at 60° C. for 1 h and then a solution of methyl 1-(3-oxopropyl)-1H-indole-7-carboxylate (278 mg, 1.2 mmol) from Step B above in 1,4-dioxane (20 mL) was added, followed by glacial acetic acid (1% of total solvent used). The reaction mixture was stirred at 60° C. for 2 h and cooled to room temperature. Sodium triacetoxyborohydride (763 mg, 3.6 mmol) was then added in portions and the reaction mixture was stirred at room temperature for 4 h. The solvent was removed under reduced pressure and the crude material was purified by column chromatography (silica gel, 80:18:2 methylene chloride/methanol/concentrated ammonium hydroxide) to give (R)-methyl 1-(3-(quinuclidin-3-ylamino)propyl)-1H-indole-7-carboxylate (317 mg, 77%) as a yellow oil: 1H NMR (300 MHz, CD3OD) δ 7.78 (d, J=13.0 Hz, 1H), 7.62 (d, J=12.5 Hz, 1H), 7.30 (d, J=5.0 Hz, 1H), 7.10 (t, J=13.0 Hz, 1H), 6.56 (d, J=5.5 Hz, 1H), 4.49 (t, J=11.5 Hz, 2H), 3.96 (s, 3H), 3.07-2.99 (m, 1H), 2.82-2.65 (m, 5H), 2.44-2.27 (m, 3H), 1.89-1.64 (m, 5H), 1.53-1.32 (m, 2H).

Provenance & Evidence