Sodium hydride → 2,12-Dimethyl-7-isocyano-2,12-di-p-tolyl-7-(toluene-4-sulfonyl)-tridecanedioic acid diethyl ester

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Reaction Steps

To a solution of 6-bromo-2-methyl-2-p-tolyl-hexanoic acid ethyl ester (21 g, 64.22 mmol), tetra-n-butylammonium iodide (2.37 g, 6.42 mmol), and p-toluene-sulphonylmethyl isocyanide (TosMIC, 6.26g, 32.11 mmol) in anhydrous DMSO (320 mL) and anhydrous diethyl ether (110 mL) was added sodium hydride (60% dispersion in mineral oil, 3.24 g, 80.92 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 combined organic layers were washed with brine (2×300 mL), dried over MgSO4, and concentrated to furnish a crude 2,12-dimethyl-7-isocyano-2,12-di-p-tolyl-7-(toluene-4-sulfonyl)-tridecanedioic acid diethyl ester A solution of this crude intermediate in CH2Cl2 (500 mL) and concd HCl (140 mL) was 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 organic layers were washed with saturated NaHCO3 solution (150 mL), and brine (150 mL), dried over MgSO4, and concentrated in vacuo. The resulting crude oil was purified by flash chromatography (silica gel, ethyl acetate/hexanes=1/20, 1/10) to furnish 2,12-dimethyl-7-oxo-2,12-di-p-tolyl-tridecanedioic acid diethyl ester (9.0 g, 67.12%) as a light yellowish oil. 1H NMR (300 MHz, CDCl3/TMS): δ (ppm) 7.10 (d, 4H, J=7.9 Hz), 7.02 (d, 4H, J=7.9 Hz), 4.05 (q, 4H, J=7.0 Hz), 2.25 (t, J=9 Hz, 4H), 2.20 (s, 6H), 1.95-1.70 (m, 4H), 1.42 (s, 6H), 1.50-1.05 (m, 8H), 1.08 (t, 6H, J=7.0 Hz). 13C NMR (75 MHz, CDCl3/TMS): δ (ppm) 211.10, 176.00, 141.00, 135.80, 128.50, 124.51, 60.50, 49.50, 42.01, 39.50, 24.05, 22.10, 20.50, 13.00. HRMS (LSIMS, nba): Calcd. for C33H47O5 (MH+): 523.3424, found: 523.3405.

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