Benzyl ether protection of an alcohol; Ether
SyntheticPage 309
DOI:
10.1039/SP309
Submitted May 27, 2009, published May 27, 2009
Chemicals Used
Benzyl trichloroacetimidate (Aldrich)
Trifluoromethanesulfonic acid (Alfa Aesar)
Dichloromethane (Distilled over Calcium Hydride)
Cyclohexane (Fischer Scientific)
Roche ester (Aldrich)
Procedure
Benzyl 2,2,2-trichloroacetimidate (2.23 mL, 12.0 mmol, 1.2 equiv.) was added dropwise to a stirred solution of (S)-3-hydroxy-2-methylpropionic acid methyl ester (1.11 mL, 10.0 mmol) in cyclohexane:dicholoromethane (2:1, 15 mL) at 0 °C. Trifluoromethanesulfonic acid (53 µL, 1 mmol, 0.1 equiv.) was then added dropwise and the reaction mixture was slowly allowed to warm to rt. After stirring for 20 h, the reaction mixture was filtered and washed with dicholoromethane (2 × 15 mL). The filtrate was washed with sat. aq. sodium bicarbonate (20 mL) and sat. brine (20 mL), then dried (magnesium sulphate), filtered and concentrated in vacuo. The crude product was purified by flash column chromatography (Petrol:Ether, 99:1 to 98:2) to afford (S)-methyl 3-(benzyloxy)-2-methylpropanoate (2.05 g, 98%) as a clear oil.
Author's Comments
Further addition of benzyl trichloroacetimidate (0.2 to 0.8 equiv.) helps accelerate the reaction. The major side product is trichloroacetamide which is a white crystalline solid and if polarity is increased beyond 98:2 (Petrol:Ether) during silica gel chromatography then it co-runs with the product.
Data
1H(400 MHz, Chloroform) 1.20 (3H, d, J 7.0), 2.72 - 2.89 (1H, m), 3.51 (1H, dd, J 9.0, 6.0), 3.67 (1H, dd, J 9.0, 7.5), 3.71 (3H, s), 4.53-4.55 (2H, m), 7.28-7.38 (5H, m); 13C(101 MHz, Chloroform) 14.0, 40.1, 51.7, 71.9, 73.1, 127.6, 127.6, 128.3, 138.1, 175.3.
Lead Reference
Zampella, A.; Sorgente, M.; D'Auria, M. V., Tetrahedron: Asymmetry, 2002, 13, 681 - 685
doi:10.1016/S0957-4166(02)00178-7
Other References
Iversen, T.; Bundle, K. R., J. Chem. Soc., Chem. Commun., 1981, 1240
doi:10.1039/c39810001240White, J. D.; Reddy, G. N.; Spessard, G. O., J. Am. Chem. Soc., 1988, 110, 1624
doi:10.1021/ja00213a047
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