Method for producing 2-acetyl-4H,9H-naphtho[2,3-b]furan-4,9-dione

Patent metadata

Field	Value
Publication number	US-10875835-B2
Application number	US-202016798833-A
Country	US
Kind code	B2
Filing date	Feb 24, 2020
Priority date	Jul 17, 2015
Publication date	Dec 29, 2020
Grant date	Dec 29, 2020

Abstract

The invention addresses the problem of providing a method for producing 2-acetyl-4H,9H-naphtho[2,3-b]furan-4,9-dione that is suited to industrial production. The invention provides a method for producing 2-acetyl-4H,9H-naphtho[2,3-b]furan-4,9-dione by reacting 3-bromo-3-buten-2-one and 2-hydroxy-1,4-naphthoquinone in the presence of a solvent, then obtaining crystals of 2-acetyl-4H,9H-naphtho[2,3-b]furan-4,9-dione by adding an alcohol-based solvent and/or water to the reaction system, and treating the crystals by using a specific adsorbent in the presence of a solvent.

First claim

The invention claimed is:

1. A production method of 2-acetyl-4H,9H-naphtho[2,3-b]furan-4,9-dione comprising the following step (d):
(d) dissolving 2-acetyl-4H,9H-naphtho[2,3-b]furan-4,9-dione in a non-alcohol-based solvent C, followed by adding an adsorbent to purify the 2-acetyl-4H,9H-naphtho[2,3-b]furan-4,9-dione.

2. The production method according to claim 1 , further comprising the following step (e) after the step (d):
(e) removing the adsorbent used in the step (d) and evaporating the non-alcohol-based solvent C.

3. The production method according to claim 2 , further comprising the following step (f) after the step (e):
(f) crystallizing 2-acetyl-4H,9H-naphtho[2,3-b]furan-4,9-dione obtained in the step (e) by adding at least one crystallization solvent D selected from the group consisting of a hydrocarbon-based solvent, an alcohol-based solvent, an acid-based solvent, an ester-based solvent, an ether-based solvent, and water, to obtain 2-acetyl-4H,9H-naphtho[2,3-b]furan-4,9-dione.

4. The production method according to claim 3 , further comprising the following step (g) after the step (f):
(g) slurrying 2-acetyl-4H,9H-naphtho[2,3-b]furan-4,9-dione obtained in the step (f) with ethyl acetate to form a crystal of 2-acetyl-4H,9H-naphtho[2,3-b]furan-4,9-dione.

5. The production method according to claim 1 , wherein the non-alcohol-based solvent C used in the step (d) is at least one selected from the group consisting of an ether-based solvent, an amide-based solvent, a ketone-based solvent, a halogen-based solvent, a sulfoxide-based solvent, an ester-based solvent, a hydrocarbon-based solvent, and a nitrile-based solvent.

6. The production method according to claim 1 , wherein the non-alcohol-based solvent C used in the step (d) is at least one selected from the group consisting of chloroform, dichloromethane, carbon tetrachloride, monochlorobenzene, N,N-dimethylacetamide, N,N-dimethylformamide, N-methyl-2-pyrrolidone, acetonitrile, propionitrile, dimethyl sulfoxide, diethyl sulfoxide, diisopropyl ether, tert-butyl methyl ether, cyclopentyl ethyl ether, cyclopentyl methyl ether, tetrahydrofuran, 2-methyltetrahydrofuran, 1,4-dioxane, anisole, methyl acetate, ethyl acetate, propyl acetate, butyl acetate, toluene, xylene, acetone, methyl ethyl ketone, and methyl isobutyl ketone.

7. The production method according to claim 1 , wherein the non-alcohol-based solvent C used in the step (d) is at least one selected from the group consisting of N,N-dimethylacetamide, N,N-dimethylformamide, anisole, ethyl acetate, propyl acetate, and butyl acetate.

8. The production method according to claim 1 , wherein the non-alcohol-based solvent C used in the step (d) is anisole.

9. The production method according to claim 1 , wherein the adsorbent used in the step (d) is at least one selected from the group consisting of activated alumina, zeolite, activated carbon, and silica gel.

10. The production method according to claim 1 , wherein the adsorbent used in the step (d) is silica gel.

11. The production method according to claim 1 , wherein the adsorbent used in the step (d) is a 0.01 to 0.3-fold amount in a weight ratio to 2-acetyl-4H,9H-naphtho[2,3-b]furan-4,9-dione.

12. The production method according to claim 11 , wherein the adsorbent used in the step (d) is a 0.02 to 0.2-fold amount in a weight ratio to 2-acetyl-4H,9H-naphtho[2,3-b]furan-4,9-dione.

13. The production method according to claim 3 , wherein the crystallization solvent D used in the step (f) is at least one selected from the group consisting of n-heptane, xylene, n-butanol, isobutyl acetate, toluene, cyclohexane, acetic acid, methanol, ethanol, 1-propanol, 2-propanol, n-butyl alcohol, isobutyl alcohol, and water.

14. The production method according to claim 3 , wherein the crystallization solvent D used in the step (f) comprises n-heptane.

15. The production method according to claim 3 , wherein the crystallization solvent D used in the step (f) comprises xylene.

16. The production method according to claim 3 , wherein the crystallization solvent D used in the step (f) comprises n-butanol.

17. The production method according to claim 3 , wherein the crystallization solvent D used in the step (f) comprises isobutyl acetate.

18. The production method according to claim 1 , wherein the purification temperature is 30° C. to 100° C.

19. The production method according to claim 1 , wherein the purification temperature is 50° C. to 90° C.

Assignees

• Sumitomo Dainippon Pharma Co Ltd

Inventors

• Yagi Toshikazu
• Suzuki Satoshi
• Tatamidani Hiroto
• Hashimoto Kazuki

Classifications

• C07D307/92 Primary

  Naphthofurans; Hydrogenated naphthofurans · CPC title

• B01J21/08

  Silica · CPC title

• C07C43/20

  having an ether-oxygen atom bound to a carbon atom of a six-membered aromatic ring · CPC title

• A61K31/343

  condensed with a carbocyclic ring, e.g. coumaran, bufuralol, befunolol, clobenfurol, amiodarone · CPC title

• A61P35/00

  Antineoplastic agents · CPC title