Uses
(S)-(-)-3-tert-Butoxycarbonyl-4-methoxycarbonyl-2,2-dimethyl-1,3-oxazolidine is a useful intermediate used in the improved synthesis of Garner′s aldehyde and analogs with multiple pharmaceutical applications.
Synthesis
To a solution of Boc-L-serine methyl ester (2a, 1.94 g, 8.85 mmol, 1.00 eq.) in dichloromethane (20.0 mL) was added 2,2-dimethoxypropane (3.25 mL, 26.6 mmol, 3.00 eq.) and boron trifluoride-ether complex (0.0553 mL, 0.443 mmol, 0.500 equivalent) in a dilute solution in dichloromethane (15.0 mL). The reaction mixture was stirred at 25 °C for 3 h and then quenched with saturated aqueous NaHCO3 solution. The aqueous layer was extracted with two portions of ethyl acetate. The combined organic layers were washed with 10% NaCl aqueous solution, dried with Na2SO4, filtered, and concentrated in vacuum. Purification of the residue by silica gel column chromatography (16% hexane solution of ethyl acetate) afforded (R)-(-)-3-BOC-4-methoxycarbonyl-2,2-dimethyl-1,3-oxazolidine (2.28 g, 8.79 mmol, 99%) as a colorless oil.
References
[1] Beilstein Journal of Organic Chemistry, 2017, vol. 13, p. 106 - 110
[2] Tetrahedron Letters, 1999, vol. 40, # 1, p. 113 - 116
[3] European Journal of Organic Chemistry, 2017, vol. 2017, # 6, p. 1045 - 1051
[4] Patent: WO2015/156601, 2015, A1. Location in patent: Page/Page column 23; 24; 25
[5] Organic Letters, 2003, vol. 5, # 23, p. 4253 - 4256
