反应详情

To a solution of 2-(6-bromo-2-methyl-2-p-tolyl-hexyloxy)-tetrahydropyran (21.5 g, 58.27 mmol), tetra-n-butylammonium iodide (2.36 g, 6.41 mmol), and p-toluenesulphonyl-methyl isocyanide (TosMIC, 5.68 g, 29.14 mmol) in anhydrous DMSO (300 mL) and anhydrous diethyl ether (100 mL) was added sodium hydride (60% dispersion in mineral oil, 2.94 g, 73.42 mmol) at rt under N2 atmosphere. The mixture was stirred for 24 h at rt. The reaction mixture was carefully hydrolized with ice-water (500 mL) and extracted with diethyl ether (2×300 mL). The organic layer was washed with brine (2×300 mL), dried over anhydrous MgSO4, and concentrated in vacuo to furnish crude 2-[7-isocyano-2,12-dimethyl-2,12-di-p-tolyl-13-(tetrahydropyran-2-yloxy)-7-(toluene-4-sulfonyl)-tridecanyloxy]-tetrahydropyran (18.44 g) as a brown oil. A solution of this crude intermediate (18 g) in methanol (300 mL), concd. HCl (36 mL), and water (70 mL) was heated to reflux for 3 h. The reaction mixture was poured into CH2Cl2 (250 mL) and ice-water (250 mL). The layers were separated and the aqueous layer was extracted with CH2Cl2 (3×100 mL). The combined organic layers were washed with saturated NaHCO3 solution (3×100 mL) and brine (150 mL), dried over anhydrous MgSO4 and concentrated in vacuo. The resulting crude oil was purified by flash chromatography (silica gel, ethyl acetate/hexanes=20/1, 15/1, 10/1, 5/1, and 1/1) to furnish 1,13-dihydroxy-2,12-dimethyl-2,12-di-p-tolyl-tridecan-7-one (2.72 g, 26.2% over two steps) as a colorless oil. 1H NMR (300 MHz, CDCl3/TMS): δ (ppm) 7.18 (d, 4H, J=8.1 Hz), 7.12 (d, 4H, J=8.1 Hz), 3.63 (d, J=11.0 Hz, 2H), 3.49 (d, J=1.0 Hz, 2H), 2.31 (s, 6H), 2.26 (t, J=7.8 Hz, 4H), 1.78-1.40 (m, 10H), 1.28 (s, 6H), 1.24-0.82 (m, 4H). 13C NMR (75 MHz, CDCl3/TMS): δ (ppm) 211.51, 141.75, 135.64, 129.23, 126.64, 72.54, 43.06, 42.65, 38.28, 24.53, 23.59, 21.66, 20.98. HRMS (LSIMS, nba): Calcd. for C29H43O3 (MH+): 439.3212, found: 439.3222.

1. extractionextracted with diethyl ether (2×300 mL)
2. washThe organic layer was washed with brine (2×300 mL)
3. dry with materialdried over anhydrous MgSO4
4. concentrationconcentrated in vacuo