At -78 °C, 22.1 mL of n-butyllithium (35.4 mmol, 1.6 M hexane solution) was slowly added dropwise to a solution of 4.91 mL (35.0 mmol) of diisopropylamine in 45 mL of tetrahydrofuran, and the mixture was stirred at -78 °C for 10 minutes, followed by 25 minutes at 0 °C. Then, 5.00 g (34.7 mmol) of methyl tetrahydro-2H-pyran-4-carboxylate in a solution in 45 mL of tetrahydrofuran was added at -78 °C and the mixture continued to be stirred at -78 °C for 15 minutes. Next, 2.16 mL (34.7 mmol) of iodomethane was added dropwise at -78 °C and the reaction mixture was slowly warmed to -25 °C and stirred overnight at room temperature. Upon completion of the reaction, the reaction was terminated by the addition of 80 mL of 0.1 N hydrochloric acid and the organic and aqueous phases were separated. The aqueous phase was extracted twice with ethyl acetate, the organic phases were combined, dried with magnesium sulfate, filtered and concentrated under reduced pressure. The resulting suspension was ground with 20 mL of methyl tert-butyl ether, the precipitate was extracted, and the mother liquor was concentrated under reduced pressure to obtain methyl 4-methyl-tetrahydro-2H-pyran-4-carboxylate. Yield: 5.88 g (purity 95%, quantitative yield).1H NMR (400 MHz, DMSO-d6) δ (ppm): 3.70-3.64 (m, 2H), 3.64 (s, 3H), 3.37-3.30 (m, 2H), 1.94-1.88 (m, 2H), 1.45-1.37 (m, 2H), 1.16 (s 3H).
