Method for preparing 4-cyanopiperidine hydrochloride

Patent metadata

Field	Value
Publication number	US-10150731-B2
Application number	US-201615542715-A
Country	US
Kind code	B2
Filing date	Jan 13, 2016
Priority date	Jan 16, 2015
Publication date	Dec 11, 2018
Grant date	Dec 11, 2018

Abstract

The present invention describes a novel method for preparing 4-cyanopiperidine hydrochloride.

First claim

The invention claimed is:

1. A method for preparing 4-cyanopiperidine hydrochloride of formula (I),

in high yield and with high purity, wherein isonipecotamide (II)

is dehydrated with thionyl chloride in a diluent in the presence of a formamide of formula (III), wherein the formamide of formula (III) is defined as follows:

R 1 , R 2 are mutually independently hydrogen, C 1 -C 6 -alkyl, C 6 -C 10 -aryl or together form a —CH 2 —CH 2 —X n —CH 2 —CH 2 — residue, in which
X is CH 2 , oxygen or sulphur
and
n is 0 or 1, and
wherein the diluent is toluene, ortho-xylene, meta-xylene, para-xylene, methyl acetate, ethyl acetate, n-propyl acetate, isopropyl acetate, n-butyl acetate or mixtures thereof.

2. A method according to claim 1 , wherein the formamide of formula (III) is defined as follows:
R 1 , R 2 are mutually independently hydrogen, methyl, ethyl, 1-propyl, 2-propyl, 1-butyl, 2-butyl, isobutyl, tertiary butyl or together form a —CH 2 —CH 2 —X n —CH 2 —CH 2 residue;
X is CH 2 or oxygen,
and
n is 0 or 1.

3. A method for preparing 4-cyanopiperidine hydrochloride of formula (I),

in high yield and with high purity, wherein isonipecotamide (II)

is dehydrated with thionyl chloride in a diluent in the presence of a formamide of formula (III), wherein the formamide of formula (III) is defined as follows:

R 1 , R 2 are 1-butyl.

4. A method according to claim 1 , wherein 1 to 5 mol equivalents of thionyl chloride are used, based on isonipecotamide.

5. A method according to claim 1 , wherein 0.1 to 3 mol equivalents of formamide are used, based on isonipecotamide.

6. A method according to claim 1 , wherein the reactant isonipecotamide has a water content of less than 5%.

7. A method according to claim 3 , wherein the diluent is toluene, ortho-xylene, meta-xylene, para-xylene, methyl acetate, ethyl acetate, n-propyl acetate, isopropyl acetate, n-butyl acetate or mixtures thereof.

8. A method according to claim 1 , wherein the yield of the 4-cyanopiperidine hydrochloride is at least 73%.

9. A method according to claim 1 , wherein the purity of the 4-cyanopiperidine hydrochloride is at least 81%.

10. A method according to claim 1 , wherein one or both of R 1 and R 2 are hydrogen.

11. A method according to claim 1 , wherein one or both of R 1 and R 2 are mutually independently C 1 -C 6 -alkyl.

12. A method according to claim 1 , wherein one or both of R 1 and R 2 are mutually independently C 6 -C 10 -aryl.

13. A method according to claim 1 , wherein R 1 and R 2 together form a —CH 2 —CH 2 —X n —CH 2 —CH 2 .

14. A method according to claim 13 , wherein:
n is 0.

15. A method according to claim 13 , wherein:
n is 1.

16. A method according to claim 15 , wherein:
X is CH 2 .

17. A method according to claim 15 , wherein:
X is oxygen.

18. A method according to claim 15 , wherein:
X is sulphur.

19. A method according to claim 1 , wherein the diluent is toluene, n-propyl acetate, or n-butyl acetate.

20. A method according to claim 1 , wherein the reactant isonipecotamide has a water content of less than 2%.

Assignees

• Bayer Cropscience Ag

Inventors

• Himmler Thomas
• Brohm Dirk

Classifications

• C07D211/62 Primary

  attached in position 4 · CPC title

• A61K31/4465

  only substituted in position 4 · CPC title