反应详情

Preparation of 1-(2-Furyl)-7-hydroxy-1-heptanone (R=n-C6H12OH)—Magnesium turnings (8.20 g, 0.342 mol, 4.5 eq/halide) were covered with anhydrous THF (40 mL) and a solution of 1-(tetrahydropyran-2-yloxy)-6-hexyl bromide (20.1 g, 76.0 mmol in anhydrous 100 mL THF) was added dropwise once the reaction was initiated with 1,2-dibromoethane. The remaining halide solution was added dropwise and the mixture was allowed to stir at rt overnight. The resulting mixture was then added to a cooled solution of the Weinreb amide (10.3 g, 66.1 mmol in 100 mL anhydrous THF, 0° C.) via cannula. The resulting slurry was stirred (3 h) and then quenched with equal amounts of 1 N HCl and H2O. After warming to rt the mixture was separated and the aqueous layer was extracted with Et2O (2×). The combined organics were washed with sat'd. NaHCO3, brine, dried (Na2SO4), filtered, and evaporated to yield crude residue, which was then dissolved in MeOH (200 mL) with a small amount of TsOH and allowed to stir overnight. The reaction mixture was stirred with NaHCO3, evaporated, and the residue taken up in hexane. The hexane portion was washed with H2O (2×), brine, dried (Na2SO4), and concentrated to yield crude furyl ketone, which was distilled under vacuum (b.p. 164–167° C., 0.2 mm Hg) to give pure furyl ketone (6.95 g, 35.4 mmol, Yld. 53.6%). 1H NMR: δ 7.57 (dd, 1H, 3JH,H=1.7 Hz, 4JH,H=0.74 Hz, H-2), 7.17 (dd, 1H, 3JH,H=3.6 Hz, 4JH,H=0.76 Hz, H-4), 6.52 (dd, 1H, 3JH,H=3.6 Hz, 3JH,H=1.7 Hz, H-3), 3.63 (t, 2H, 3JH,H=6.6 Hz, H-12), 2.81 (t, 2H, 3JH,H=7.6 Hz, H-7), 2.13 (bs, 1H, OH), 1.72 (quintet, 2H, 3JH,H=7.4 Hz, H-8), 1.57 (quintet, 2H, 3JH,H=6.7 Hz, H-11), 1.39 (m, 4H, H-9 and 10). 13C NMR: δ 189.8, 152.7, 146.3, 117.0, 112.2, 62.8, 38.3, 32.5, 29.0, 25.5, 24.2.

1. customPreparation of 1-(2-Furyl)-7-hydroxy-1-heptanone (R=n-C6H12OH)—Magnesium turnings (8.20 g, 0.342 mol, 4.5 eq/halide)
2. stirringThe resulting slurry was stirred (3 h)
3. customquenched with equal amounts of 1 N HCl and H2O
4. temperatureAfter warming to rt the mixture
5. customwas separated
6. extractionthe aqueous layer was extracted with Et2O (2×)
7. washThe combined organics were washed with sat'd
8. dry with materialNaHCO3, brine, dried (Na2SO4)
9. filtrationfiltered
10. customevaporated
11. customto yield crude residue, which
12. stirringto stir overnight
13. customevaporated
14. washThe hexane portion was washed with H2O (2×), brine
15. dry with materialdried (Na2SO4)
16. concentrationconcentrated
17. customto yield crude furyl ketone, which
18. distillationwas distilled under vacuum (b.p. 164–167° C., 0.2 mm Hg)