Crystallization of 25-hydroxy-7-dehydrocholesterol

Patent metadata

Field	Value
Publication number	US-10316055-B2
Application number	US-201615774697-A
Country	US
Kind code	B2
Filing date	Nov 28, 2016
Priority date	Nov 30, 2015
Publication date	Jun 11, 2019
Grant date	Jun 11, 2019

Abstract

The present invention relates to a method of purification of compound of formula (I) which comprises the step of crystallization of compound of formula (I) from a composition comprising the compound of formula (I) and the compound of formula (II) and a specific solvent system containing ethanol, 1-propanol, 2-propanol, 2-methyl-1-propanol, 1-butanol or 2-butanol.

First claim

The invention claimed is:

1. A method for purifying a compound of formula (I) from a composition comprising the compound of formula (I) and a the compound of formula (II) in a solvent system:

wherein the method comprises the steps of:
a) dissolving a composition comprising a compound of formula (I) and a compound of formula (II) at temperature (T sol ) above 40° C. in a crystallization solvent system to yield a solution A comprising the compound of formula (I) and of the compound of formula (II);
b) cooling the solution A comprising the compound of formula (I) and the compound of formula (II) obtained by step a) to a temperature (T cool ) of 30° C. or below to yield crystals of the compound of formula (I); and
c) isolating the crystals of the compound of formula (I), and wherein the solvent system is either:
i) ethanol, 1-propanol, 2-propanol, 2-methyl-1-propanol, 1-butanol or 2-butanol; or
ii) a binary, tertiary or quaternary mixture of ethanol, 1-propanol, 2-propanol, 2-methyl-1-propanol, 1-butanol or 2-butanol; or
iii) a mixture of solvents selected from the group consisting of ethanol, 1-propanol, 2-propanol, 2-methyl-1-propanol, 1-butanol and 2-butanol with methanol and/or with a C 5 -C 6 alcohol, with the proviso that the total amount of ethanol, 1-propanol, 2-propanol, 2-methyl-1-propanol, 1-butanol and 2-butanol is equal to or more than 50% by weight of the solvent system.

2. The method according to claim 1 , wherein the solvent system comprises ethanol, 1-propanol or 2-propanol.

3. The method according to claim 1 , wherein the solvent system is 2-propanol.

4. The method according to claim 1 , wherein the solvent system comprises a solvent mixture selected from the group consisting of methanol/2-propanol; methanol/1-propanol; methanol/1-propanol/2-propanol and methanol/ethanol/2-propanol.

5. The method according to claim 1 , wherein the solvent system comprises a mixture of solvents selected from the group consisting of ethanol, 1-propanol, 2-propanol, 2-methyl-1-propanol, 1-butanol and 2-butanol with methanol and/or with a C 5 -C 6 alcohol, with the proviso that the total amount of ethanol, 1-propanol, 2-propanol, 2-methyl-1-propanol, 1-butanol and 2-butanol is more than 60% by weight.

6. The method according to claim 1 , wherein the temperature (T sol ) in step a) is above 60° C.

7. The method according to claim 1 , wherein the temperature (T cool ) in step b) is in the range of −10° C. to 15° C.

8. The method according to claim 1 , wherein the method comprises two or more crystallization cycles.

9. The method according to claim 1 , wherein the method of purification results in purifying the compound of formula (I) such that the compound of formula (II) is present as an impurity in an amount of less than 0.40% by weight, relative to the weight of the compound of formula (I).

10. A composition comprising a compound of formula (I) and a compound of formula (II):

wherein the amount of the compound of formula (II) in the composition is at most 0.40% by weight, relative to the weight of the compound of formula (I).

11. The method according to claim 1 , wherein the temperature (T sol ) in step a) is at the boiling temperature of the solvent system to at most 10° C. lower than the boiling temperature of the solvent system as measured at 1013 mbar.

12. The method according to claim 11 , wherein the temperature (T sol ) in step a) is at most 5° C. lower than the boiling temperature of the solvent system as measured at 1013 mbar.

13. The method according to claim 1 , wherein the temperature (T cool ) in step b) is in the range of 0° C. to 10° C.

Assignees

• Dsm Ip Assets Bv

Inventors

• Schuetz Jan
• Waechter Ralph

Classifications

• B01D9/005

  Selection of auxiliary, e.g. for control of crystallisation nuclei, of crystal growth, of adherence to walls; Arrangements for introduction thereof · CPC title

• B01D2009/0086

  Processes or apparatus therefor · CPC title

• B01D9/0063

  Control or regulation (control per se G05) · CPC title

• C07J9/00 Primary

  Normal steroids containing carbon, hydrogen, halogen or oxygen substituted in position 17 beta by a chain of more than two carbon atoms, e.g. cholane, cholestane, coprostane · CPC title