Method for preparing a non-radioactive standard β-CFT

Patent metadata

Field	Value
Publication number	US-11466002-B2
Application number	US-202117225269-A
Country	US
Kind code	B2
Filing date	Apr 8, 2021
Priority date	Oct 21, 2020
Publication date	Oct 11, 2022
Grant date	Oct 11, 2022

Abstract

This invention discloses method for preparing a non-radioactive standard β-CFT. Using cocaine hydrochloride as the starting material, and after a series of hydrolysis, dehydration, esterification and bonding reactions, a non-radioactive standard (2β-Carbomethoxy-3β-(4-fluoropenyl) tropane) is prepared. Furthermore, this preparation method has fewer steps, is easy to operate, and the purity of the product is as high as 97.97%. Therefore, the method for preparing a non-radioactive standard β-CFT can promote the development of positron imaging in the diagnosis of Parkinson's disease.

First claim

What is claimed is:

1. A preparing method of non-radioactive standard β-CFT, the steps include:
Taking a cocaine hydrochloride and a hydrochloric acid for a hydrolysis reaction to form an ecgonine hydrochloride;
Taking the ecgonine hydrochloride and a phosphorus oxychloride for a dehydration reaction to form a (R)-(-)-Anhydroecgonine methyl ester; and
And taking the (R)-(-)-Anhydroecgonine methyl ester and a Grignard reagent making a bonding reaction to form a 2β-Carbomethoxy-3β-(4-fluoropenyl) tropane.

2. The preparing method of non-radioactive standard β-CFT stated in claim 1 , wherein after the step of taking the ecgonine hydrochloride and a phosphorus oxychloride for a dehydration reaction, it further comprises the step of: adding an anhydrous methanol for an esterification reaction.

3. The preparing method of non-radioactive standard β-CFT stated in claim 1 , wherein in the step of taking the (R)-(-)-Anhydroecgonine methyl ester and a Grignard reagent for a bonding reaction, the Grignard reagent is a 4-fluorophenyl magnesium bromide.

4. The preparing method of non-radioactive standard β-CFT stated in claim 3 , wherein before the step of taking the (R)-(-)-dehydrated ecgonine methyl ester and a Grignard reagent for a bonding reaction, the method further includes the step of: dissolving the Grignard reagent in anhydrous dichloromethane, and cooling it down to −50° C.

5. The preparing method of non-radioactive standard β-CFT stated in claim 3 , wherein in the step of taking the (R)-(-)-dehydrated ecgonine methyl ester and a Grignard reagent for a bonding reaction, the bonding reaction is carried out under nitrogen environment.

6. The preparing method of non-radioactive standard β-CFT stated in claim 3 , wherein in the step of taking the (R)-(-)-dehydrated ecgonine methyl ester and a Grignard reagent for a bonding reaction, a trifluoroacetic acid is further added for the bonding reaction.

Assignees

• Iner Aec Executive Yuan

Inventors

• Lee Ching Yun
• Chang Yu

Classifications

• C07D451/02 Primary

  containing not further condensed 8-azabicyclo [3.2.1] octane or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane; Cyclic acetals thereof · CPC title

• C07B49/00

  Grignard reactions · CPC title