ABSTRACT
Entrv % Catalvst Solvent Yield a:p ratio
1 5 TPPHBr CH,C1? 75 2:1
2 5 TPPHBr MeCN 86 4:1
3 10 TPPHBr MeCN 81 8:1
4 20 TPPHBr MeCN 81 9:1
5 50 TPPHBr MeCN 82 10:1
6 20 TPPHBr DME 81 10:1
7 20 aq.HBr (48%w/w) DME 53 5:1
8 5 aq.HBr (48%w/w) DME 38 2:1
9 5 aq.HBr (48%w/w) MeCN 64 4:1
10 20 HBr DME Mixture 3:1
11 20 HBr MeCN 93 5:1
Scheme 12: Proposed mechanism of direct methanolysis of TADG (17)
As DME is less toxic than acetonitrile this was selected as the solvent of choice using the
conditions of entry 6, Table 2. As the mixture of anomers (48) and their hydrolysed products were
Thus, after reaction with TPPHBr and methanol, neutralisation of excess acid together with the
simultaneous methanolysis of the three acetyl groups were performed by addition of 0.3
equivalents of sodium methoxide solution. After stirring for one hour the excess sodium
methoxide was quenched with 0.2 equivalents of triethylamine hydrochloride. This effected the
neutralisation without the formation of water. Any residual methanol was removed by
displacement of the solvents by co-distillation with toluene. Tritylation was carried out by addition
of 3 equivalents of triethylamine and 1 equivalent of trityl chloride, stirring at 45°C for 12 hours.
