Method for producing intermediate of biotin and method for producing biotin

Patent metadata

Field	Value
Publication number	US-10689349-B2
Application number	US-201716322511-A
Country	US
Kind code	B2
Filing date	Jul 26, 2017
Priority date	Aug 4, 2016
Publication date	Jun 23, 2020
Grant date	Jun 23, 2020

Abstract

In the method, a trione compound represented by the following formula (1) is (i) reduced by NaAlH 2 (OCH 2 CH 2 OCH 3 ) 2 and subsequently further reduced by a metal borohydride salt, or (ii) reduced by calcium borohydride, thereby producing an amide alcohol compound represented by the following formula (3) (wherein, R 1 and R 2 may be the same or different and each represents a hydrogen atom or a protecting group of an ureylene group; R 4 represents an alkyl group, an aralkyl group, or an aryl group; and each of R 5 , R 6 , and R 7 represents a hydrogen atom, an alkyl group, an alkoxy group, or a halogen atom).

First claim

What is claimed is:

1. A method for producing a lactone compound in which an ureido compound represented by the following formula (11)

wherein, R 1 and R 2 may be the same or different and represent a hydrogen atom or a protecting group of an ureylene group, is dehydrated by refluxing in a reaction solvent comprising mesitylene, thereby producing an anhydride compound represented by the following formula (7)

the anhydride compound and an optically active amine compound represented by the following formula (8)

wherein, R 4 represents an alkyl group, an aralkyl group, or an aryl group, and each of R 5 , R 6 , and R 7 represents a hydrogen atom, an alkyl group, an alkoxy group, or a halogen atom, are reacted in a reaction solvent comprising mesitylene, thereby producing a mixture which comprises an amide compound I represented by the following formula (9)

and an amide compound II represented by the following formula (10)

a first reaction solution comprising the obtained mixture and mesitylene is refluxed to dehydrate the mixture, thereby producing a trione compound represented by the following formula (1)

the trione compound is (ii) reduced by calcium borohydride in ethanol, thereby producing an amide alcohol compound represented by the following formula (3)

and the amide alcohol compound is cyclized in the presence of hydrogen chloride in a solvent comprising an alkylene glycol monoalkyl ether in which the total number of carbon atoms in a molecule is 2 to 12, thereby producing a lactone compound represented by the following formula (4)

2. A method for producing an amide alcohol compound in which a trione compound represented by the following formula (1)

wherein, R 1 and R 2 may be the same or different and each represents a hydrogen atom or a protecting group of an ureylene group;
R 4 represents an alkyl group, an aralkyl group, or an aryl group; and
each of R 5 , R 6 , and R 7 represents a hydrogen atom, an alkyl group, an alkoxy group, or a halogen atom is
(ii) reduced by calcium borohydride in ethanol, thereby producing an amide alcohol compound represented by the following formula (3)

3. A method in which
an amide alcohol compound represented by the formula (3) is produced by the method according to claim 2 , and
subsequently the amide alcohol compound is cyclized in the presence of hydrogen chloride in a solvent comprising an alkylene glycol monoalkyl ether in which the total number of carbon atoms in a molecule is 2 to 12, thereby producing a lactone compound represented by the following formula (4)

4. A method in which
a lactone compound represented by the formula (4) is produced by the method according to claim 3 , and
subsequently the lactone compound is reacted with a thiation agent, thereby producing a thiolactone compound represented by the following formula (5)

5. A method in which
after producing a thiolactone compound represented by the formula (5) by the method according to claim 4 ,
the thiolactone compound is used as a raw material to produce biotin represented by the following formula (6)

6. The method according to claim 2 , wherein an anhydride compound represented by the following formula (7)

and an optically active amine compound represented by the following formula (8)

are reacted in a reaction solvent comprising mesitylene, thereby producing a mixture which comprises an amide compound I represented by the following formula (9)

and an amide compound II represented by the following formula (10)

a first reaction solution comprising the obtained mixture and mesitylene is refluxed to dehydrate the mixture, thereby producing the trione compound represented by the formula (1); and
subsequently the obtained trione compound is (ii) reduced by calcium borohydride in ethanol, thereby producing the amide alcohol compound represented by the formula (3).

7. The method according to claim 6 , wherein an ureido compound represented by the following formula (11)

is dehydrated by refluxing in a reaction solvent comprising mesitylene, thereby producing the anhydride compound represented by the formula (7); and
subsequently the obtained anhydride compound is reacted with the optically active amine compound represented by the formula (8).

8. The method according to claim 1 , wherein a reaction temperature at the time of reducing by the calcium borohydride in (ii) is −30° C. or more and 50° C. or less.

9. The method according to claim 1 , wherein the total number of carbon atoms in a molecule of the alkylene glycol monoalkyl ether is 2 to 6.

10. The method according to claim 1 , wherein
a second reaction solution which comprises the anhydride compound represented by the formula (7) and a reaction solvent comprising mesitylene is produced; and
subsequently the second reaction solution and the optically active amine compound represented by the formula (8) are mixed, thereby producing the mixture which comprises the amide compound I represented by the formula (9) and the amide compound II represented by the formula (10).

11. The method according to claim 3 , wherein the total number of carbon atoms in a molecule of the alkylene glycol monoalkyl ether is 2 to 6.

12. The method according to claim 6 , wherein
a second reaction solution which comprises the anhydride compound represented by the formula (7) and a reaction solvent comprising mesitylene is produced; and
subsequently the second reaction solution and the optically active amine compound represented by the formula (8) are mixed, thereby producing the mixture which comprises the amide compound I represented by the formula (9) and the amide compound II represented by the formula (10).

13. A meth

Assignees

• Tokuyama Corp

Inventors

• Iwasaki Fumiaki
• Yamamoto Hiromasa
• Tanaka Kenji
• Seki Masahiko
• Seike Yoshiki

Classifications

• Y02P20/55

  Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups · CPC title

• C07D491/048 Primary

  the oxygen-containing ring being five-membered · CPC title

• A61P3/10

  for hyperglycaemia, e.g. antidiabetics · CPC title

• C07D487/04

  Ortho-condensed systems · CPC title

• C07D233/34 Primary

  Ethylene-urea · CPC title