18-Crown-6 → Tert-butyl 3-((5-cyclopropyl-3-((trans)-2-(trifluoromethyl)cyclohexyl)isoxazol-4-yl)methoxy)-8-azabicyclo[3.2.1]octane-8-carboxylate

Participants

Reaction Steps

A solution of N-Boc-nortropine (579 mg, 2.55 mmol) and 18-crown-6 (808 mg, 3.06 mmol) in THF (8.5 mL) was treated with potassium tert-butoxide (343 mg, 3.06 mmol) and stirred for 10 minutes. A solution of 4-(chloromethyl)-5-cyclopropyl-3-((trans)-2-(trifluoromethyl)cyclohexyl)isoxazole (784 mg, 2.55 mmol) in THF was added. The resulting mixture was stirred at rt for 2 hours and then poured into water and extracted with EtOAc. Organics were collected, dried (MgSO4), filtered, concentrated and chromatographed (SiO2, linear gradient, 0-60% EtOAc in Hexanes) to give the title compound. 1H NMR (400 MHz, CDCl3) δ 4.28 (m, 2H), 4.19 (m, 1H), 4.11 (m, 1H), 3.66 (dd, J=4.8, 4.7 Hz, 1H), 3.47 (dd, J=7.6, 3.7 Hz, 1H), 2.42 (m, 1H), 2.19 (ddd, J=25.2, 12.5, 3.4 Hz, 1H), 2.00-1.77 (m, 13H), 1.69 (m, 1H), 1.52 (m, 1H), 1.46 (s, 9H), 1.35 (m, 1H), 1.12 (m, 2H), 1.03 (m, 2H)4; MS m/z 443.2 (M-tBu+1).

Provenance & Evidence