Reaction Steps
In a 250 mL round bottom flask, 9.5 mL of n-butyl lithium (2.5 M solution in hexane, 23.8 mmol) was added via a syringe to a pre-cooled solution (−78° C.) of 2-(2-methylbut-3-yn-2-yloxy)-tetrahydro-2H-pyran 2 (4.0 g, 23.8 mmol) in 100 mL of Et2O. The resulting solution was stirred for 30 min at −78° C., then ethyl 2,2-diethoxyacetate (4.9 g, 27.7 mmol) was added with a syringe, and the stirring continued for 12 hours. The reaction mixture was poured in an ice-cold saturated aqueous solution of NH4Cl. The aqueous layer was extracted with Et2O (3×50 mL). The organic solvent was separated with a separating funnel and dried with anhydrous MgSO4. The solvent was removed under reduced pressure and the resulting pale yellow oil was purified by radial chromatography (stationary phase silica gel, hexane/AcOEt 90:10) to provide 1,1-diethoxy-5-methyl-5-(tetrahydro-2H-pyran-2-yloxy)hex-3-yn-2-one 3 as a colorless liquid. Yield: 3.2 g (10.7 mmol; 45%). 1H-NMR in CDCl3 (δ, ppm): 5.05 (1H, q, J=5.0, 3.5 Hz, THP), 4.73 (1H, s, acetal), 3.92 (1H, m, THP), 3.69 (2H, m, CH2, acetal), 3.62 (2H, m, CH2, acetal), 3.50 (1H, m, THP), 1.82 (1H, m, THP), 1.71 (1H, m, THP), 1.58 (3H, s, CH3), 1.54 (3H, s, CH3), 1.52 (4H, m, THP), 1.25 (6H, t, J=7.0 Hz, CH3, acetal). 13C-NMR in CDCl3 (δ, ppm): 182.6, 101.1, 97.87, 96.10, 81.25, 70.57, 62.95, 62.64, 62.61, 31.47, 29.45, 28.85, 25.06, 19.92, 14.90 IR (neat, cm−1): 2978, 2937, 2872, 2214, 1687, 1074. HR ESIMS+ with acetonitrile as the mobile phase, (m/z): 299.1837 (M+, C16H26O5, 299.1853), 321.1660 (m/z) ([M+Na]+, C16H26O5Na, 321.1672).
