Deprotection method for protected hydroxyl group
View Patent ↗To deprotect an alcoholic hydroxyl group protected by a t-butyldimethylsilyl group without influencing a functional group unstable to an acid. In the presence of a solvent, an alcohol having a hydroxyl group protected by a t-butyldimethylsilyl group is deprotected in the presence of an acid or an acid salt having a pKa of from 1.0 to 3.0 in water.
1. A method to remove the t-butyldimethylsilyl group from a t-butyldimethylsilyl ether compound of a secondary or tertiary alcohol, comprising:
preparing a reaction mixture by adding the t-butyldimethylsilyl ether compound and an acid substance to a mixture of water and a solvent selected from the group consisting of a nitrile, an amide and an ester;
hydrolyzing the t-butyldimethylsilyl ether compound to obtain the secondary or tertiary alcohol; and
isolating the secondary or tertiary alcohol from the hydrolyzed reaction mixture;
wherein
the acid substance is selected from the group consisting of an organic acid, a salt of an organic acid, an inorganic acid and a salt of an inorganic acid; and
a pKa of the acid substance in water is from 1.0 to 3.0.
2. The method according to claim 1 , wherein the isolation comprises:
adding water or an aqueous sodium chloride solution to the hydrolyzed reaction mixture; and
extracting the secondary or tertiary alcohol from the aqueous phase with an organic solvent.
3. The method according to claim 1 , wherein the acid substance is a carboxylic acid.
4. The method according to claim 3 , wherein the carboxylic acid comprises at least two carboxyl groups per molecule.
5. The method according to claim 3 , wherein the carboxylic acid is oxalic acid or maleic acid.
6. The method according to claim 1 , wherein a proportion of water in the mixed solvent is 0.01≦water/(organic solvent+water)≦0.8 by volume ratio.
7. The method according to claim 1 , wherein the hydrolysis reaction temperature is from 0 to 100° C.
8. The method according to claim 1 , wherein the secondary or tertiary alcohol comprises at least one moiety unstable to an acid, selected from the group consisting of a vinyl ether moiety, an allyl ether moiety, an allyl alcohol moiety, an acetal moiety, a beta-hydroxycarbonyl moiety, a tetrahydropyranyloxy group, an epoxy group, an amide bond, an ester bond and a polyene moiety.
9. The method of claim 1 , wherein the organic solvent is selected from the group consisting of N,N-dimethylformamide, N,N-dimethylacetamide, N-methylpyrrolidone, N,N-dimethylimidazoline, ethyl acetate, acetonitrile and propionitrile.
10. The method of claim 1 , wherein the mixture of water and solvent is free of tetrahydrofuran.
11. A method to remove the t-butyldimethylsilyl group from a t-butyldimethylsilyl ether compound of an alcohol, comprising:
preparing a reaction mixture by adding the t-butyldimethylsilyl ether compound and an acid substance to a mixture of water and a solvent selected from the group consisting of a nitrile, an amide and an ester:
hydrolyzing the t-butyldimethylsilyl ether compound to obtain the alcohol; and
isolating the alcohol from the hydrolyzed reaction mixture;
wherein
the acid substance is selected from the group consisting of an organic acid, a salt of an organic acid, an inorganic acid and a salt of an inorganic acid:
a pKa of the acid substance in water is from 1.0 to 3.0,
the mixture of water and the solvent is free of tetrahydrofuran.