반응 #76256
ord-3139919290b14b198fc806fc2f839c9d
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후처리
- 1온도under cooling in a water-bath
- 2온도while cooling in a water-bath
- 3온도under cooling in a water-bath
- 4기타The layers were separated
- 5추출the aqueous layer was extracted with dichloromethane (3×100 mL)
- 6세척The combined organic layers were washed with water (2×200 mL) and saturated NaCl solution (100 mL)
- 7건조dried over MgSO4
- 8농축concentrated in vacuo
- 9기타dried in high vacuo
실험 절차
Under N2 atmosphere, to a solution of 5-bromo-1-(tetrahydropyranyloxy)-2,2-dimethylpentane (40.0 g, 0.143 mol) and p-toluenesulphonylmethyl isocyanide (TosMIC; 13.99 g, 0.072 mol) in anhydrous DMSO (400 mL) was added sodium hydride (60% dispersion in mineral oil, 6.86 g, 0.173 mol) under cooling in a water-bath. Tetra-n-butylammonium iodide (5.28 g, 0.0143 mol) was then added while cooling in a water-bath. The mixture was stirred for 6 h at rt., then carefully hydrolyzed by drop-wise addition of water (100 mL) under cooling in a water-bath. The reaction mixture was diluted with dichloromethane (100 mL), additional water (100 mL), and dichloromethane (100 mL). The layers were separated and the aqueous layer was extracted with dichloromethane (3×100 mL). The combined organic layers were washed with water (2×200 mL) and saturated NaCl solution (100 mL), dried over MgSO4, concentrated in vacuo, and dried in high vacuo to give crude 2-[6-isocyano-2,2,10,10-tetramethyl-11-(tetrahydropyran-2-yloxy)-6-(toluene-4-sulfonyl)-undecyloxy]-tetrahydropyran (47.9 g) as a brownish, viscous oil. This crude oil (47.0 g) was dissolved in methanol (200 mL) and water (40 mL). Concentrated sulfuric acid (20 mL) was added drop-wise over 10 min whereupon the solution warmed up to ca. 30° C. The reaction mixture was stirred at rt for ca. 150 min and then diluted with water (200 mL). The mixture was extracted with CH2Cl2 (2×200 mL, 1×100 mL) and the combined organic layers were washed with water (200 mL), 10% potassium hydroxide solution (3×200 mL), water (200 mL), and brine (160 mL). The organic extracts were dried over MgSO4, concentrated in vacuo, and dried in high vacuo to furnish crude 1,11-dihydroxy-2,2,10,10-tetramethyl-undecan-6-one (26.0 g) as a brown oil. The crude product was purified by chromatography (silica, 330 g, hexanes/ethyl acetate=90/10, 70/30, 50/50) to obtain three fractions: A: 1.1 g, 93.5% purity by HPLC, 5.6% yield; B: 3.0 g, ca. 96.7% purity by HPLC, 16% yield, and C: 4.0 g, ≧90% purity by NMR, 19.5%. Fraction C was again purified by chromatography (silica, 150 g, hexanes/ethyl acetate=60/40) to give clean product (1.5 g, purity by HPLC: 96.3%). Overall yield: 5.6 g, 30.3% over two steps. 1H NMR (300 MHz, CDCl3/TMS): δ (ppm) 3.25 (s, 4H), 2.60 (br., 2H), 2.32 (t, 4H, J=7.2), 1.45 (m, 4H), 1.12 (m, 4H), 0.79 (s, 12H). 13C NMR (75 MHz, CDCl3=77.0 ppm/TMS): δ (ppm) 212.25, 70.99, 43.15, 37.69, 34.94, 23.89, 17.91. HRMS (LSIMS, gly): Calc for C15H29O2 (MH+—H2O): 241.2168, found: 241.2169.