Furan → 2-Furanyl(3-(tert-butoxycarbonyl)-3-azabicyclo[3.3.1]non-7-yl)methanone

Participants

Reaction Conditions

Reaction Steps

To a suspension of N,O-dimethylhydroxylamine hydrochloride (0.068 g 0.70 mmol) in anhydrous THF (3 mL) was added trimethylaluminum (2.0 M solution in toluene, 0.35 mL, 0.70 mmol) at −10° C. After stirring for 10 min at −10° C., a solution of methyl (3-(tert-butoxycarbonyl)-3-azabicyclo[3.3.1]nonane-7-carboxylate (0.100 g, 0.353 mmol) in THF (1 mL) was added. The reaction mixture was warmed to ambient temperature and stirred for 1 h. The reaction was then cooled to −70° C. and was treated with a freshly prepared 2-furanyllithium in THF (5 mL) solution (Note: the 2-furanyllithium was prepared by treating furan (0.24 g, 3.5 mmol) with n-BuLi (2.5 M solution in THF, 1.4 mL, 3.5 mmol) at −78° C.). The reaction mixture was warmed to ambient temperature over 1 h and quenched with saturated aqueous ammonium chloride solution (5 mL). The volatiles were removed in vacuo, and the residue was triturated with ethyl acetate (2×10 mL). The combined organic extracts were dried over anhydrous sodium sulfate, concentrated under reduced pressure and purified by HPLC, to yield 2-furanyl(3-(tert-butoxycarbonyl)-3-azabicyclo[3.3.1]non-7-yl)methanone (0.018 g, 16% yield). A portion of this material (4.5 mg, 14 μmol) was dissolved in a 1:1 mixture of anhydrous dichloromethane and TFA. After stirring for 1 h at ambient temperature, the volatiles were evaporated, and the resulting residue was dried on high vacuum to yield 3.2 mg (68% yield) of 2-furanyl(3-azabicyclo[3.3.1]non-7-yl)methanone trifluoroacetate as a pale yellow oil (1H NMR (CD3OD): δ 7.68 (s, 1H), 6.75 (d, J=2.68 Hz, 1H), 6.58 (m, 1H), 4.16-4.11 (m, 1H), 3.52-3.14 (m 3H), 2.64-2.57 (m 1H), 2.25-1.87 (m, 8H) (LC/MS (MH+): 220).

Provenance & Evidence