Acetone → Methyl-2,3-O-isopropylidene-D-ribofuranoside

In the first part of the transformation the glycol group of ribose is protected using 2,2-dimethoxy propane and/or acetone in methanol in the presence of catalytic amounts of acid. The intermediate ((3aR,4R,6aR)-6-methoxy-2,2-dimethyltetrahydrofuro[3,4-d][1,3]dioxol-4-yl)-methanol (B) is not isolated in a pure state, but the reaction is treated by a base, preferably selected from the base used in the next step, most preferably pyridine. Most of volatile compounds solvents are then removed, the residue is extracted by an organic solvent selected from chlorinated hydrocarbons, esters or ethers, preferably by methyl tert-butyl ether, the extract is optionally dried and solution is concentrated and diluted by a pyridine type solvent, selected from pyridine, picolines or lutidine, preferably by pyridine. The obtained mixture is sulfonated by an addition of a chloride or anhydride of a sulfonic acid selected from unsubstituted or fluoro substituted C1-C4-alkanesulfonic acids, or unsubstituted or methyl, methoxy, bromo, nitro substituted, preferably para substituted benzenesulfonic acids, or camphor-10-sulfonic acid, followed by demoisturing with drying agent such as sodium or magnesium sulfate and removal of solvent under reduced pressure. The sulfonates of formula C, such as ((3aR,4R,6aR)-6-methoxy-2,2-dimethyltetrahydrofuro[3,4-d][1,3]dioxol-4-yl)methyl 4-methylbenzenesulfonate (C′, compound C, R′=p-tolyl) or ((3aR,4R,6aR)-6-methoxy-2,2-dimethyl-tetrahydrofuro[3,4-d][1,3]dioxol-4-yl)methyl methanesulfonate (C″, compound C, R′=Me) are solid crystalline materials, which are optionally purified by recrystallization from appropriate solvent such as 2-propanol to give very pure compounds.

ORD record

ord-e5ec3bd2593c4ac38e5af02b0a3dfaf8

Source dataset

uspto-grants-2016_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09278972B2