Synthesis
In a typical synthesis, 73 mL of acetic anhydride (780 mmol) was mixed with 63 mL of pyridine (780 mmol) in a round-bottomed flask and cooled in an ice bath.After 5-10 min, 8.6 g (100 mmol) of L-methionine methyl ester hydrochloride was added to the reaction mixture, which was then allowed to slowly rise to room temperature and stirred overnight. The following day, the reaction was quenched with cold water and extracted four times with 75 mL of dichloromethane. The combined organic phases were sequentially washed three times each with 1 M hydrochloric acid, saturated sodium bicarbonate solution and water. The organic layer was subsequently dried with anhydrous magnesium sulfate, filtered and concentrated under reduced pressure to give a yellow oil, which crystallized on standing. The crude product was purified by recrystallization from ether at -20°C. The crystals were collected by vacuum filtration to give the product 19.3 g (94 mmol, 94% yield). The melting point was 41.7-42.4 °C. 1H NMR ([2H]-chloroform, TMS as internal standard, δ 0.0 ppm): δ 1.86-2.20 (m, 2H), δ 2.00 (s, 3H), δ 2.05 (s, 3H), δ 2.45-2.60 (m, 2H), δ 3.75 (s, 3H), δ 4.62-4.70 (m, 1H) , δ 6.13-6.19 (bd, 1H).
References
[1] Tetrahedron Asymmetry, 2011, vol. 22, # 3, p. 283 - 293
[2] Chemical and pharmaceutical bulletin, 1986, vol. 34, # 3, p. 986 - 998
