Process for the preparation of d,1-2-(6-methoxy-2-naphthyl)propionic acid
AssigneeSyntex (U.S.A.) Inc.
InventorCharles A. Dvorak
Life of this patent
Estimating the term…
Abstract
Racemic mixtures of d,1-2-(6-methoxy-2-naphthyl)propanal are resolved by forming a condensation product with N-R-D-glucamine or a salt thereof where R is hydrogen, alkyl of 1 to 36 carbon atoms or cycloalkyl of 3 to 8 carbon atoms, from which a product substantially enriched in d-2-(6-methoxy-2-naphthyl)propanal can be obtained and then can be selectively oxidized to d-2-(6-methoxy-2-naphthyl)propionic acid.
Claims17
A process for isolating a condensation product of d-2-(6-methoxy-2-naphthyl)propanal comprising
- crystallizing the condensation product of d-2-(6-methoxy-2-naphthyl)propanal with N-R-D-glucamine or a salt thereof wherein R is hydrogen, alkyl of 1 to 36 carbon atoms or cycloalkyl of 3 to 8 carbon atoms from a mixture containing a first condensation product of d-2-(6-methoxy-2-naphthyl)propanal with N-R-D-glucamine or a salt thereof and a second condensation product of 1-2-(6-methoxy-2-naphthyl)propanal with N-R-D-glucamine or a salt thereof in an inert solvent, the first condensation product being significantly less soluble in the inert solvent than the second condensation product at the crystallization temperature of the first condensation product.
A process for preparing a condensation product of d-2-(6-methoxy-2-naphthyl)propanal comprising
- reacting a racemic mixture of d,1-2-(6-methoxy-2-naphthyl)propanal with N-R-D-glucamine or a salt thereof wherein R is hydrogen, alkyl of 1 to 36 carbon atoms or cycloalkyl of 3 to 8 carbon atoms in an inert solvent to form a mixture of a first condensation product of d-2-(6-methoxy-2-naphthyl)propanal with N-R-D-glucamine or a salt thereof and a second condensation product of 1-2-(6-methoxy-2-naphthyl)propanal with N-R-D-glucamine or a salt thereof, the first condensation product being significantly less soluble in the inert solvent than the second condensation product at the crystallization temperature of the first condensation product;
- and
- crystallizing the first condensation product from the mixture to yield a product enriched in the first condensation product.
A process for preparing d-2-(6-methoxy-2-naphthyl)propionic acid comprising
- crystallizing the condensation product of d-2-(6-methoxy-2-naphthyl)propanal with N-R-D-glucamine or a salt thereof wherein R is hydrogen, alkyl of 1 to 36 carbon atoms or cycloalkyl of 3 to 8 carbon atoms from a mixture containing a first condensation product of d-2-(6-methoxy-2-naphthyl)propanal with N-R-D-glucamine or a salt thereof and a second condensation product of 1-2-(6-methoxy-2-naphthyl)propanal with N-R-D-glucamine or a salt thereof in an inert solvent, the first condensation product being significantly less soluble in the inert solvent than the second condensation product at the crystallization temperature of the first condensation product;
- hydrolyzing the first condensation product to obtain d-2-(6-methoxy-2-naphthyl)propanal;
- and
- oxidizing d-2-(6-methoxy-2-naphthyl)propanal to obtain d-2-(6-methoxy-2-naphthyl)propionic acid.
A process for preparing d-2-(6-methoxy-2-naphthyl)propionic acid comprising
- reacting a racemic mixture of d,1-2-(6-methoxy-2-naphthyl)propanal with N-R-D-glucamine or a salt thereof wherein R is hydrogen, alkyl of 1 to 36 carbon atoms or cycloalkyl of 3 to 8 carbon atoms in an inert solvent to form a mixture of a first condensation product of d-2-(6-methoxy-2-naphthyl)propanal with N-R-D-glucamine or a salt thereof and a second condensation product of 1-2-(6-methoxy-2-naphthyl)propanal with N-R-D-glucamine or a salt thereof, the first condensation product being significantly less soluble in the inert solvent than the second condensation product at the crystallization temperature of the first condensation product;
- crystallizing the first condensation product from the mixture to yield a product enriched in the first condensation product;
- hydrolyzing the first condensation product to obtain d-2-(6-methoxy-2-naphthyl)propanal;
- and
- oxidizing d-2-(6-methoxy-2-naphthyl)propanal to obtain d-2-(6-methoxy-2-naphthyl)propionic acid.
A process for preparing d-2-(6-methoxy-2-naphthyl)propionic acid comprising
- hydrolyzing a condensation product of d-2-(6-methoxy-2-naphthyl)propanal with N-R-D-glucamine or a salt thereof wherein R is hydrogen, alkyl of 1 to 36 carbon atoms or cycloalkyl of 3 to 8 carbon atoms to obtain d-2-(6-methoxy-2-naphthyl)propanal;
- and
- oxidizing d-2-(6-methoxy-2-naphthyl)propanal to obtain d-2-(6-methoxy-2-naphthyl)propionic acid.
A mixture of the condensation product of d,1-2-(6-methoxy-2-naphthyl)propanal with N-R-D-glucamine or a salt thereof, wherein R is hydrogen, alkyl of 1 to 36 carbon atoms or cycloalkyl of 3 to 8 carbon atoms.
A resolving medium comprising a mixture of a first condensation product of d-2-(6-methoxy-2-naphthyl)propanal with N-R-D-glucamine or a salt thereof and a second condensation product of 1-2-(6-methoxy-2-naphthyl)propanal with N-R-D-glucamine or a salt thereof wherein R is hydrogen, alkyl of 1 to 36 carbon atoms or cycloalkyl of 3 to 8 carbon atoms, and a solvent in which the first condensation product is less soluble than the second condensation product to permit fractional crystallization of said condensation products upon the cooling of said medium from an elevated temperature.
Dependencies are inferred from the claim text.