Process for preparing optically active α-hydroxy acids and derivatives thereof
AssigneeHardy W. Chan
InventorsBiing-Jiun Uang, Jia-Wen Chang, Der-Pin Jang
Life of this patent
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Abstract
The present invention provides a process for preparing optically active α-hydroxy acids and derivatives thereof by subjecting the alkylated 1,3-dioxolanones of formula (IV) wherein R1 and R2 are the same or different and are each independently H or C1-6 alkyl; R5 is H, C1-16 alkyl, or unsubstituted or substituted phenyl; and R6 is C1-8 alkyl, C2-7 alkenyl or unsubstituted or substituted benzyl, to either alcoholysis or hydrolysis, in which the alkylated 1,3-dioxolanones are obtained by using 10-camphorsulfonamide as a chiral auxiliary.
Claims12
A process for preparing α-hydroxy acids and derivatives thereof, comprising the step of subjecting the alkylated 1,3-dioxolanones of formula IV
- wherein R1 and R2 are the same or different and are each independently H or C1-6 alkyl;
- R5 is H, C1-16 alkyl, or unsubstituted or substituted phenyl;
- and R6 is C1-8 alkyl, C2-7 alkenyl or unsubstituted or substituted benzyl, to either
- (i) alcoholysis, when R5 is H, to form α-hydroxy acids derivatives of formula V
- wherein R6 is C1-8 alkyl, C2-7 alkenyl or unsubstituted or substituted benzyl, and R7 is C1-6 alkyl, and isolating the resulting product;
- or
- (ii) hydrolysis, when R5 is C1-16 alkyl or unsubstituted or substituted phenyl, to form α-hydroxy acids of formula VI
- wherein R5 is H, C1-16 alkyl, or unsubstituted or substituted phenyl;
- and R6 is C1-8 alkyl, C2-7 alkenyl or unsubstituted or substituted benzyl, and isolating the resulting products (V) and (VI).
A process for preparing optically active α-hydroxy acids, comprising steps
- (a) reacting 10-camphorsulfonamide of formula I
- wherein R1 and R2 are the same or different and are each independently H or C1-6 alkyl,
- with alkoxy-substituted alkane in the presence of an alcohol and p-toluene sulfonic acid to form dialkoxy acetal of formula II
- wherein R1 and R2 are the same or different and are each independently H or C1-6 alkyl, and R3 and R4 are the same or different and are each independently C1-4 alkyl;
- (b) reacting the dialkoxy acetal of formula II with an α-hydroxy acid having the formula
- wherein R5 is H, C1-16 alkyl, or unsubstituted or substituted phenyl, in the presence of an ether and a Lewis acid to form the 1,3-dioxolanones of formula III
- wherein R1 and R2 are the same or different and are each independently H or C1-6 alkyl, and R5 is H, C1-16 alkyl, or unsubstituted or substituted phenyl;
- (c) reacting the 1,3-dioxolanones of formula III with alkylation reagents in the presence of a strong base and optionally of hexamethyl phosphoramide under the temperature in the range between −100° C. to 0° C. to form the alkylated 1,3-dioxolanones of formula IV
- wherein R1 and R2 are the same or different and are each independently H or C1-6 alkyl, R5 is H, C1-6 alkyl, or unsubstituted or substituted phenyl, and R6 is C1-8 alkyl, C2-7 alkenyl or unsubstituted or substituted benzyl;
- (d) subjecting the alkylated, 1,3-dioxolanones of formula IV to either
- (i) alcoholysis, when R5 is H, to form α-hydroxy acids derivatives of formula V
- wherein R6 is C1-8 alkyl, C2-7 alkenyl or unsubstituted or substituted benzyl, and R7 is C1-6 alkyl, or
- (ii) hydrolysis, when R5 is C1-16 alkyl or unsubstituted or substituted phenyl, to form α-hydroxy acids of formula VI
- wherein R5 is H, C1-16 alkyl, or unsubstituted or substituted phenyl, and R6 is C1-8 alkyl, C2-7 alkenyl or unsubstituted or substituted benzyl, and recovering the 10-camphorsulfonamide of formula I.
Dependencies are inferred from the claim text.