초록 ▼

The present invention provides a method for making glycoside compounds including the steps of: (a) lithiating an aromatic reactant having a leaving group using a lithium reagent in a first microreactor under non-cryogenic conditions to form a lithiated anion species, and (b) coupling the lithiated a

The present invention provides a method for making glycoside compounds including the steps of: (a) lithiating an aromatic reactant having a leaving group using a lithium reagent in a first microreactor under non-cryogenic conditions to form a lithiated anion species, and (b) coupling the lithiated anion species with a carbonyl substituted reactant to form a glycoside.

대표청구항 ▼

What is claimed is: 1. A method of making glycosides using a non-cryogenic process comprising, in a continuous process, the steps of: (a) lithiating an aromatic reactant having a leaving group using a lithium reagent in a first microreactor at non-cryogenic temperatures to form a lithiated anion sp

What is claimed is: 1. A method of making glycosides using a non-cryogenic process comprising, in a continuous process, the steps of: (a) lithiating an aromatic reactant having a leaving group using a lithium reagent in a first microreactor at non-cryogenic temperatures to form a lithiated anion species; and (b) coupling the lithiated anion species with a carbonyl substituted reactant at non-cryogenic temperatures to form a glycoside. 2. The method according to claim 1, wherein said lithiating step is performed at a temperature of from about-10° C. to about 20° C. 3. The method according to claim 2, wherein said lithiating step is performed at a temperature of from about-10° C. to about 5° C. 4. The method according to claim 1, wherein the residence time in said first microreactor is from about 2 seconds to about 3 seconds. 5. The method according to claim 1, wherein said aromatic reactant is a halide. 6. The method according to claim 1, where said lithium reagent is selected from the group consisting of n-BuLi and t-BuLi. 7. The method according to claim 1, wherein said coupling step is performed in a second microreactor under non-cryogenic conditions. 8. The method according to claim 7, wherein said coupling step is performed at a temperature of from about-20° C. to about 20° C. 9. The method according to claim 8, wherein said coupling step is performed at a temperature of about-10° C. 10. The method according to claim 7, wherein the residence time in said second microreactor is from about 2 seconds to about 3 seconds. 11. The method according to claim 7, wherein a yield of said glycoside is greater than about 70%. 12. A method of making glycosides using a non-cryogenic process comprising, in a continuous process, the steps of: (a) lithiating an aromatic reactant having a leaving group wing a lithium reagent at non-cryogenic temperatures to form a lithiated anion species; and (b) coupling the lithiated anion species with a carbonyl substituted reactant according to formula IV wherein X1 is a heteroatom; R2 is a substituted or unsubstituted alkyl group; and PG is a protective group, in a microreactor under non-cryogenic temperatures to form a glycoside. 13. The method according to claim 12, wherein said coupling step is performed at a temperature of from about-10° C. to about 200° C. 14. The method according to claim 12, wherein said coupling step is performed at a temperature of from about-10° C. to about 5° C. 15. The method according to claim 12, wherein the residence time in said microreactor is from about 2 seconds to about 3 seconds. 16. The method according to claim 12, further comprising the step of: (c) deprotecting the glycoside. 17. A continuous process for making a glycoside having the general structural formula [I]: wherein: R1 is hydrogen, NO2, OR4, a halogen, or a substituted or non-substituted alkyl , aryl, or heterocycle; R2 is a substituted or non-substituted alkyl group; R4 is a substituted or non-substituted alkyl or aryl; X1 is a heteroatom; and PG is a protective group, the method including the steps of: (a) reacting an aromatic reactant having general structural formula [II]: wherein: R1 is as defined previously and X2 is a leaving group, in a first microreactor with an organo lithium reagent at non-cryogenic temperatures to form a lithiated anion species having general structural formula [III]: wherein R1 is as defined previously, and (b) coupling the lithiated anion species [III] with a carbonyl substituted compound having general structural formula [IV] : wherein: R2, X1 and PG are as described previously, at non-cryogenic temperatures to form the compound having general structural formula [I]. 18. The method of claim 17 wherein the lithiating step is performed at a temperature of from about-10° C. to 20° C. 19. The method of claim 18 wherein the coupling step is performed in a second microreactor at non-cryogenic temperatures. 20. The method of claim 18 wherein the lithiating step is conducted in a solvent selected from THF/toluene or THF/heptane. 21. The method of claim 18 wherein the coupling step is performed in a second microreactor at non-cryogenic temperatures. 22. The method of claim 21 wherein the coupling step is performed at a temperature of from about-20° C. to 20° C. 23. The method of claim 12 wherein PG is a per(silyl) group. 24. The method of claim 23 wherein PG is Me3Si, Et3Si or Me2SiBu-t. 25. The method of claim 17 wherein PG is a per(silyl) group. 26. The method of claim 25 wherein PG is Me3Si, Et3Si or Me2SiBu-t.