Manufacture of alpha-arylalkanoic acids and precursors
AssigneeSyntex Pharmaceuticals International Ltd.
InventorGeorge C. Schloemer
Life of this patent
Estimating the term…
Abstract
.alpha.-Arylalkanoic acids or esters, orthoesters or amides thereof are prepared by forming an .alpha.-hydroxy ketal or thioketal of an aryl alkyl ketone, activating the .alpha.-hydroxy substituent with an esterifying agent to form the corresponding ketal or thioketal ester substrate, wherein the ester group is sufficiently labile to non-catalytically disassociate from the substrate in a protic or dipolar, aprotic solvent, maintaining the ester substrate in contact with the protic or dipolar, aprotic solvent or mixtures thereof for a time sufficient to form the corresponding .alpha.-arylakanoic acid or ester, orthoester or amide thereof, and optionally concomitantly or sequentially hydrolyzing any ester, orthoester or amide formed to the corresponding .alpha.-arylalkanoic acid.
Claims19
A process for preparing an .alpha.-arylalkanoic acid of the formula ##STR17## or an ester, orthoester or amide thereof wherein Ar is an aryl moiety and R.sub.1 is lower alkyl having 1-8 carbon atoms inclusive or cycloalkyl having 3-7 carbon atoms inclusive, which comprises:
- contacting a ketal or thioketal of a compound of the formula ##STR18## wherein Ar and R.sub.1 are as defined above with an esterifying agent to form the corresponding ketal or thioketal ester substrate of the compound of the formula ##STR19## wherein Ar and R.sub.1 are as defined above and -O-Z is the anionic residue of an organic acid and is sufficiently labile to disassociate from the ester substrate upon contact with a protic or dipolar, aprotic solvent, maintaining said ester substrate in contact with said protic or dipolar, aprotic solvent at a temperature and for a time sufficient to form the .alpha.-arylalkanoic acid or ester, orthoester or amide thereof, and optionally concomitantly or sequentially hydrolyzing any ester, orthoester or amide formed to the corresponding .alpha.-arylalkanoic acid.
A process for preparing an .alpha.-arylalkanoic acid of the formula ##STR21## or an ester, ortho ester or amide thereof wherein Ar is an aryl moiety and R.sub.1 is lower alkyl having 1-8 carbon atoms inclusive or cycloalkyl having 3-7 carbon atoms inclusive, which comprises maintaining a ketal or thioketal of a compound of the formula:
- ##STR22## wherein Ar and R.sub.1 are as defined above and -O-Z is the anionic residue of an organic acid and is sufficiently labile to disassociate upon contact with a protic or dipolar, aprotic solvent, in contact with a protic or dipolar, aprotic solvent at a temperature and for a time sufficient to form the .alpha.-arylalkanoic acid or ester, ortho ester or amide thereof, and optionally concommitantly or sequentially hydrolyzing any ester, ortho ester or amide formed to the corresponding .alpha.-arylalkanoic acid.
The process of 13 wherein said protic and dipolar, aprotic solvents are selected from the group consisting of water, alcohols, amides, N-alkylamides, carboxylic acids, dimethylsulfide, 2,3-dioxane, carbon disulfide, acetone and mixtures thereof.
The process for preparing a compound of the formula ##STR23## or the ester, orthoester or amide thereof which comprises:
- contacting an .alpha.-hydroxy ketal of the formula ##STR24## wherein R.sub.4 and R.sub.5 are lower alkyl having 1-4 carbon atoms inclusive, with an alkyl or aryl sulfonyl halide to form the corresponding sulfonate ester of the formula ##STR25## wherein R.sub.6 is a lower alkyl having 1-4 carbon atoms inclusive, maintaining said sulfonate ester in contact with a protic or dipolar aprotic solvent at a temperature and for a time sufficient to form 2-(6-methoxy-2-naphthyl)propionic acid or an ester, orthoester or amide thereof, and
- optionally concomitantly or sequentially hydrolyzing any ester, orthoester or amide formed to 2-(6-methoxy-2-naphthyl)propionic acid.
Dependencies are inferred from the claim text.