Uses
(S)-(+)-2,2-Dimethyl-1,3-dioxolan-4-ylmethyl p-Toluenesulfonate has been used as a reactant for the synthesis of 16-(3-trifluoromethyl)phenoxy PGF2α analog travoprost (T715600) which has potent topical ocular activity. (S)-(+)-2,2-Dimethyl-1,3-dioxolan-4-ylmethyl p-Toluenesulfonate has also been used for the preparation of p38 mitogen activated protein (MAP) kinase inhibitors.
Synthesis
The general procedure for the synthesis of (S)-(2,2-dimethyl-1,3-dioxolan-4-yl)methyl 4-methylbenzenesulfonate from p-toluenesulfonyl chloride and (R)-(-)-glycerol acetonide was carried out as follows: in accordance with the methodology used for the preparation of (R)-(-)-20a, (R)-(-)-2,2-dimethyl-4-(hydroxymethyl)-1,3-dioxolan-1,3-dioxolan (19b) ( 2.50 g) was converted to (S)-(+)-3-toluenesulfonyloxy-1,2-propanediol acetone compound 20b (5.23 g, 98% yield, 99.2% ee). [α]D20 +4.5 (c 1.0, EtOH) (literature value [α]D25 +4.7 (c 1.0, EtOH)).IR, NMR, and HRMS spectroscopic data were in complete agreement with the (R)-(-)-20a enantiomer.
References
[1] Chemical and Pharmaceutical Bulletin, 1995, vol. 43, # 10, p. 1719 - 1723
[2] Journal of Medicinal Chemistry, 2010, vol. 53, # 8, p. 3198 - 3213
[3] Tetrahedron, 2013, vol. 69, # 5, p. 1634 - 1648
[4] Journal of the American Chemical Society, 1980, vol. 102, # 20, p. 6304 - 6311
[5] Journal of the Chemical Society, Chemical Communications, 1984, # 6, p. 349 - 350
