Sodium hydride → 2,10-Dimethyl-6-isocyano-6-(4-tolyl-sulfonyl)-2,10-diphenyl-undecanedioic acid diethyl ester

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Reaction Steps

To a solution of ethyl 5-bromo-2-methyl-2-phenyl-pentanoate (25 g, 75.25 mmol), tetra-ii-butylammonium iodide (2.78 g, 7.53 mmol), and p-toluenesulphonylmethyl isocyanide (TosMIC, 7.34 g, 37.63 mmol) in anhydrous DMSO (400 mL) and anhydrous diethyl ether (I150 mL) was added sodium hydride (60% dispersion in mineral oil, 3.80 g, 95 mmol) at rt under N2 atmosphere. The reaction mixture was stirred for 24 h at rt, then carefully hydrolized with ice-water (600 mL), and extracted with diethyl ether (2×300 mL). The organic layer was washed with brine (2×300 mL) dried over anhydrous MgSO4, concentrated in vacuo to furnish crude 2,10-dimethyl-6-isocyano-6-(4-tolyl-sulfonyl)-2,10-diphenyl-undecanedioic acid diethyl ester (28 g) as a brown oil. A solution of this crude intermediate (25 g) was dissolved in CH2Cl2 (500 mL) and concd. HCl (140 mL) and stirred for 2 h at rt. The reaction mixture was diluted with water (500 mL) and the layers were separated. The aqueous layer was extracted with CH2Cl2 (2×200 mL). The combined layers were washed with saturated NaHCO3 solution (150 mL), and brine (150 mL), dried over MgSO4, and concentrated ill vacuo. The resulting crude oil was purified by flash chromatography (silica gel, ethyl acetate/hexanes=1/20, 1/10) to furnish 2,10-dimethyl-6-oxo-2,10-diphenyl-undecanedioic acid diethyl ester (9.5 g, 50.3%) as a light yellowish oil. 1H NMR (300 MHz, CDCl3/TMS): δ (ppm) 7.40-7.10 (m, 10H), 4.20-4.05 (m, 4H), 2.38 (m, 4H), 2.05-1.80 (m, 4H), 1.60 (s, 6H), 1.50-1.20 (m, 4H), 1.22 (m, 6H). 13C NMR (75 MHz, CDCl3/TMS): δ (ppm) 210.24, 176.06, 143.71, 128.42, 126.72, 125.97, 60.83, 50.13, 42.97, 38.91, 22.73, 22.47, 19.09, 14.13. HRMS (LSIMS, nba): Calcd. for C29H39O5 (MH+): 467.2797, found: 467.2772.

Provenance & Evidence