Ammonium Hydroxide → Tert-butyl 2-(6-((perfluorophenoxy)sulfonyl)naphthalen-1-yl)pyrrolidine-1-carboxylate

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Reaction Conditions

Reaction Steps

A 100-mL round-bottom flask was charged with tert-butyl 1-pyrrolidinecarboxylate (Sigma-Aldrich, St. Louis, Mo., 0.774 ml, 4.41 mmol) and THF (22.07 ml) to give a clear solution. The flask was flushed with Ar (g), then cooled in a −30° C. dry ice-acetone bath for 10 min. sec-butyllithium (1.4 M in cyclohexane) (3.15 ml, 4.41 mmol) was added dropwise over 2 min. The resulting mixture was stirred for 15 min, during which time the bath had warmed to −25° C., then zinc chloride (1M in diethyl ether) (3.31 ml, 3.31 mmol) was added dropwise. The cooling bath was removed. After 25 min, a solid mixture of perfluorophenyl 5-bromonaphthalene-2-sulfonate (Intermediate M, 1.00 g, 2.207 mmol), palladium(ii) acetate (0.050 g, 0.221 mmol), and tri-tert-butylphosphonium tetrafluoroborate (0.064 g, 0.221 mmol) was added in one portion. The resulting mixture was stirred further for 2 h. A 30% aq ammonium hydroxide solution (1 mL) was added, and the mixture was stirred vigorously for 10 min. The mixture was then filtered through diatomaceous earth with the aid of ethyl acetate. The filtrate was washed with 0.5N aq. HCl, and the aq. layer was extracted with EtOAc. The combined organic layers were washed with brine, dried over magnesium sulfate, filtered, and concentrated. The residue was purified by chromatography on silica gel (40-g, 0 to 30% EtOAc/Heptane) to give tert-butyl 2-(6-((perfluorophenoxy)sulfonyl)naphthalen-1-yl)pyrrolidine-1-carboxylate (709.11 mg, 1.305 mmol, 59.1% yield) as a white solid: 1H NMR (400 MHz, DMSO-d6) δ ppm=8.85-8.73 (m, 1H), 8.49 (d, J=9.0 Hz, 1H), 8.17 (d, J=8.2 Hz, 1H), 7.99 (d, J=8.3 Hz, 1H), 7.80-7.68 (m, 1H), 7.62-7.42 (m, 1H), 5.81-5.50 (m, 1H), 3.77-3.65 (m, 1H), 3.62-3.49 (m, 1H), 1.98-1.60 (m, 3H), 1.42 (br. s., 4H), 1.29-1.19 (m, 1H), 0.92 (s, 5H); m/z (ESI) 488.2 (M+H-t-Bu)+.

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