Vanillylidenechloroacetone and its use thereof in synthesis of calebin-a

Patent metadata

Field	Value
Publication number	US-2023286893-A1
Application number	US-202318116987-A
Country	US
Kind code	A1
Filing date	Mar 3, 2023
Priority date	Mar 9, 2022
Publication date	Sep 14, 2023
Grant date	—

Abstract

The present invention discloses a compound, Vanillylidenechloroacetone (VCA)—1-Chloro-4-(4′-hydroxy-3′-methoxy-phenyl)-but-3-en-2-one, and the process of preparing the same. The invention also discloses a process for synthesis of Calebin-A from Vanillylidenechloroacetone.

First claim

1 . A compound, 1-Chloro-4-(4′-hydroxy-3′-methoxy-phenyl)-but-3-en-2-one (VCA), as represented by STR#1

2 . The compound as in claim 1 , wherein the said compound is prepared using a process comprising steps of:
a) Reacting 1,3-dichloroacetone with R 3 P in methanol at room temperature, gradually heating to above room temperature for a time period, allowing it to go for completion, and cooling to room temperature to generate a reaction mixture; b) Quenching the reaction mixture from step a) with an aqueous base and maintaining it at room temperature for 20-24 hrs; c) Processing the mixture from step b) to isolate the ylid as represented by STR#2; and

d) Refluxing the ylid from step c) with Vanillin in a solvent for 15 hours and isolating the compound VCA as represented by STR#1,

wherein VCA is isolated with an yield of not less than least 40%.

3 . The process as in claim 2 , wherein R in R 3 P is selected from the group consisting of alkyl and aryl, wherein alkyl group is C1-C4 linear or substituted, aryl group is either phenyl or substituted phenyl.

4 . The process as in claim 2 , wherein the R in R 3 P is phenyl.

5 . The process as in claim 4 , wherein R 3 P is triphenylphosphine.

6 . The process as in claim 2 , wherein above room temperature ranges from 35° C. to 70° C.

7 . The process as in claim 2 , wherein the time period ranges from 20 hours to 24 hours.

8 . The process as in claim 2 , wherein the aqueous base is selected from the group consisting of sodium hydroxide, potassium hydroxide, lithium hydroxide, calcium hydroxide; sodium carbonate, potassium carbonate, caesium carbonate, calcium carbonate, magnesium carbonate, sodium bicarbonate, potassium bicarbonate, sodium methoxide, potassium methoxide, triethylamine, tributylamine, N-methylmorpholine, N,N-diisopropylethylamine, N-methylpyrrolidine, pyridine, collidine 4-(N,N-dimethylamino)pyridine, morpholine, imidazole, 2-methylimidazole, and 4-methylimidazole.

9 . The process as in claim 2 , wherein the processing in step c) involves filtering, washing with methanol, and purification.

10 . The process as in claim 2 , wherein the solvent is selected from the group consisting of methanol, ethanol, isopropanol, acetone, methyl ethyl ketone, diethyl ketone, methyl isopropyl ketone, methyl isobutyl ketone, ether solvents, diethyl ether, diisopropyl ether, tert-butyl methyl ether, dibutyl ether, tetrahydrofuran, 1,2-dimethoxyethane, 2-methoxyethanol, 2-ethoxy ethanol, anisole, 1,4-dioxane, toluene, xylene, chlorobenzene, tetralin, chloroform, dichloromethane, water, or mixtures thereof.

11 . A process to prepare Calebin-A as represented by STR#3 from VCA, comprising steps of:
a) Reacting VCA with ferulic acid at room temperature in a solvent in the presence of a base; b) Isolating Calebin-A from step a) with a yield of at least 80%

12 . The process as in claim 11 , wherein the solvent is selected from the group consisting of methanol, ethanol, isopropanol, acetone, methyl ethyl ketone, diethyl ketone, methyl isopropyl ketone, methyl isobutyl ketone, ether solvents, diethyl ether, diisopropyl ether, tert-butyl methyl ether, dibutyl ether, tetrahydrofuran, 1,2-dimethoxyethane, 2-methoxyethanol, 2-ethoxy ethanol, anisole, 1,4-dioxane, toluene, xylene, chlorobenzene, tetralin, chloroform, dichloromethane, water, or mixtures thereof.

13 . The process as in claim 11 , wherein the base is selected from the group consisting sodium hydroxide, potassium hydroxide, lithium hydroxide, calcium hydroxide; sodium carbonate, potassium carbonate, caesium carbonate, calcium carbonate, magnesium carbonate, sodium bicarbonate, potassium bicarbonate, sodium methoxide, potassium methoxide, triethylamine, tributylamine, N-methylmorpholine, N,N-diisopropylethylamine, N-methylpyrrolidine, pyridine, collidine 4-(N,N-dimethylamino)pyridine, morpholine, imidazole, 2-methylimidazole, and 4-methylimidazole.

Assignees

• Majeed Muhammed
• Nagabhushanam Kalyanam
• Muthukaman Nagarajan
• Pentakota Paradesi Naidu

Inventors

• Majeed Muhammed
• Nagabhushanam Kalyanam
• Muthukaman Nagarajan
• Pentakota Paradesi Naidu

Classifications

• C07C49/255 Primary

  containing ether groups, [IMAGE cpc-sch-C07C-0958.gif] groups,[IMAGE cpc-sch-C07C-0959.gif] groups, or[IMAGE cpc-sch-C07C-0960.gif] groups · CPC title

• C07C67/10

  by reacting carboxylic acids or symmetrical anhydrides with ester groups or with a carbon-halogen bond (preparation from carboxylic acid halides C07C67/14) · CPC title

• C07C45/69

  by addition to carbon-to-carbon double or triple bonds · CPC title

• C07C45/68

  by increase in the number of carbon atoms · CPC title