Carbon Dioxide → 1-Chloro-4-(beta-glucopyranos-1-yl)-2-(4-hydroxybenzyl)-benzene

Temperature

-80 °C

A solution of 4.0 g [4-(5-bromo-2-chloro-benzyl)-phenoxy]-tert-butyl-dimethyl-silane in 42 ml dry diethyl ether is cooled to −80° C. under argon. 11.6 ml of a 1.7 M solution of tert-butyllithium in pentane are slowly added dropwise to the cooled solution, and then the solution is stirred for 30 min at −80° C. This solution is then added dropwise through a transfer needle, which is cooled with dry ice, to a solution of 4.78 g 2,3,4,6-tetrakis-O-(trimethylsilyl)-D-glucopyranone in 38 ml diethyl ether chilled to −80° C. The resulting solution is stirred for 3 h at −78° C. Then a solution of 1.1 ml methanesulfonic acid in 35 ml of methanol is added and the solution is stirred for 16 h at ambient temperature. The solution is then neutralised with solid sodium hydrogen carbonate, ethyl acetate is added and the methanol is removed together with the ether. Aqueous sodium hydrogen carbonate solution is added to the remaining solution which is extracted four times with ethyl acetate. The organic phases are dried over sodium sulfate and evaporated down. The residue is dissolved in 30 ml acetonitrile and 30 ml dichloromethane and the solution is cooled to −10° C. After the addition of 4.4 ml triethylsilane 2.6 ml boron trifluoride etherate are added dropwise so that the temperature does not exceed −5° C. After the addition is complete the solution is stirred for another 5 h at −5 to −10° C. and then quenched by the addition of aqueous sodium hydrogen carbonate solution. The organic phase is separated off and the aqueous phase is extracted four times with ethyl acetate. The combined organic phase are dried over sodium sulfate, the solvent is removed and the residue is purified using silica gel. The product then obtained is an approx. 6:1 mixture of β/α which can be converted into the pure β-anomer by global acetylation of the hydroxy groups with acetic anhydride and pyridine in dichloromethane and recrystallising the product in ethanol. The product thus obtained is converted into the title compound by reacting in methanol with 4 M potassium hydroxide solution.

1. additionThis solution is then added dropwise through a transfer needle, which
2. temperaturechilled to −80° C
3. stirringThe resulting solution is stirred for 3 h at −78° C
4. stirringthe solution is stirred for 16 h at ambient temperature
5. additionis added
6. customthe methanol is removed together with the ether
7. additionAqueous sodium hydrogen carbonate solution is added to the remaining solution which
8. extractionis extracted four times with ethyl acetate
9. dry with materialThe organic phases are dried over sodium sulfate
10. customevaporated down
11. dissolutionThe residue is dissolved in 30 ml acetonitrile
12. temperature30 ml dichloromethane and the solution is cooled to −10° C
13. additionAfter the addition of 4.4 ml triethylsilane 2.6 ml boron trifluoride etherate
14. additionare added dropwise so that the temperature
15. customdoes not exceed −5° C
16. additionAfter the addition
17. stirringis stirred for another 5 h at −5 to −10° C.
18. customquenched by the addition of aqueous sodium hydrogen carbonate solution
19. customThe organic phase is separated off
20. extractionthe aqueous phase is extracted four times with ethyl acetate
21. dry with materialThe combined organic phase are dried over sodium sulfate
22. customthe solvent is removed
23. customthe residue is purified
24. customThe product then obtained
25. additionan approx. 6:1 mixture of β/α which
26. customrecrystallising the product in ethanol
27. customThe product thus obtained

ORD record

ord-9f34458010c74fafbbb84d464a5f8562

Source dataset

uspto-grants-2010_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07772378B2