Reaction Steps
Sodium hydride (60% in mineral oil, 73.7 mg, 1.92 mmol) is added portionwise to a cooled (0° C.) solution containing 13 (569 mg, 1.78 mmol), cyclopropyl isothiocyanate (500 μL, 5.40 mmol), and dimethylformamide (5.0 mL). The resulting mixture was allowed to warm to room temperature with stirring overnight (18.5 h). Methyl iodide (700 μL, 11.22 mmol) is added to the resulting solution to give a precipitate within minutes. The mixture is stirred for an additional 24 h. The reaction mixture is quenched by addition of a saturated aqueous solution of ammonium chloride (50 mL) and extracted with ethyl acetate (3×100 mL). The combined organic extracts are washed with brine (200 mL), dried over magnesium sulfate, and evaporated under reduced pressure to give the crude product. This material is purified by flash column chromatography (eluting with 10% v/v ethyl acetate in methylene chloride; Rf 0.59) to give 586.0 mg (76% yield) of 14 as a viscous yellow oil. 1H NMR (CDCl3): δ 0.86 (m, 2H, c-Pr CH2), 0.89 (t, JH-H=7.0 Hz, CO2CH2CH3), 0.98 (m, 2H, c-Pr CH2), 2.52 (s, 3H, S—CH3), 3.01 (m, 1H, c-Pr CH), 3.90 (q, JH-H=7.0 Hz, 2H, CO2CH2CH3), 3.94 (d, JH-F=1.5 Hz, 3H, OCH3), 6.97 (dd, JH-H=8.5 Hz, JH-F=6.5 Hz, 1H, aromatic H-6), 7.30 (dd, JH-H=8.5 Hz, JH-F=1.5 Hz, 1H, aromatic H-5), 11.91 (br, 1H, OH). 19F{1H} NMR (CDCl3): 8-130.4 (s). 13C{1H} NMR (CDCl3): δ 8.6 (c-Pr CH2), 13.5 (CO2CH2CH3), 18.1 (S—CH3), 28.5 (c-Pr CH), 60.3 (CO2CH2CH3), 61.4 (d, JC-F=5.0 Hz, OCH3), 104.2 (—C(OH)═C(CO2CH2CH3)—), 118.3 (d, JC-F=2.5 Hz, aromatic C-4), 123.4 (d, JC-F=3.5 Hz, aromatic C-6), 127.6 (d, JC-F=3.5 Hz, aromatic C-5), 131.9 (d, JC-F=14.5 Hz, aromatic C-1), 145.1 (d, JC-F=13.5 Hz, aromatic C-3), 152.6 (d, JC-F=253.0 Hz, C-2), 167.7 (CO2CH2CH3), 174.5 (—N═C(S—CH3)—), 185.5 (—C(OH)═C(CO2CH2CH3)—). LCMS m/z calcd for C17H1979BrFNO4S ([M]+) 431. Found 432 ([M+H]+). HRMS m/z calcd for C17H2079BrFNO4S 432.0280 ([M+H]+). Found 432.0276.
