Uses
2,3,4,6-Tetrakis-O-trimethylsilyl-D-gluconolactone is an antidiabetic agent and an intermediate of Dapagliflozin (D185370). 2,3,4,6-Tetrakis-O-trimethylsilyl-D-gluconolactone acts as a reagent in the synthesis of trans-cyclohexane-bearing C-glucose as sodium glucose co-transporter 2 inhibitors.
Synthesis
At present, the publicly reported synthesis process of 2,3,4,6-Tetrakis-O-trimethylsilyl-D-gluconolactone is mainly prepared by the synthesis of D-gluconolactone and trimethylsilyl chloride in the presence of an acid-binding agent or the preparation of D-gluconolactone and hexamethyldisilazane in dichloromethane reflux. The former has problems such as high pH requirements, low atom economy, and severe pollution. In contrast, the latter has such problems as the large amount of hexamethyldisilazane used, the strong volatility of dichloroethane, and severe pollution. Therefore, Li et al. developed a method for preparing 2,3,4,6-Tetrakis-O-trimethylsilyl-D-gluconolactone, comprising the following operations: reacting D-gluconolactone with hexamethyldisilazane in an ionic liquid at standard pressure, and removing the ionic liquid by reduced pressure distillation after the reaction is completed to obtain 2,3,4,6-Tetrakis-O-trimethylsilyl-D-gluconolactone; the cation in the ionic liquid is an alkyl imidazolium ion, and the anion in the ionic liquid is hexafluorophosphate, tetrafluoroborate, tetrachloroaluminate or chloride ion.
References
[1] Patent: US2011/237789, 2011, A1. Location in patent: Page/Page column 11-12
[2] Patent: US2011/237526, 2011, A1. Location in patent: Page/Page column 7; 8
[3] Patent: US2013/267694, 2013, A1. Location in patent: Page/Page column 0297-0301
[4] Patent: WO2015/43473, 2015, A1. Location in patent: Paragraph 00113
[5] Patent: US2015/191502, 2015, A1. Location in patent: Paragraph 0084
