Method for making fluorine labeled L-Dopa

• US 7,022,872 B2
• Filed: 12/19/2003
• Issued: 04/04/2006
• Est. Priority Date: 12/19/2003
• Status: Active Grant

• Current Assignee: Siemens Medical Solutions USA Incorporated (Siemens AG)
• Original Assignee: Molecular Technologies
• Inventors: Walsh, Joseph C., Padgett, Henry C.
• Primary Examiner(s): Dentz, Bernard
• Application Number:
  US10/742,023
• Publication Number:
  US 20050137421A1
• Time in Patent Office: 837 Days
• Field of Search: 560/8, 560/19, 560/205, 560/29, 560/39
• US Class Current: 560/39
• CPC Class Codes: C07B 2200/05 Isotopically modified compounds, e.g. labelled
• CPC Class Codes: C07B 2200/07 Optical isomers
• CPC Class Codes: C07C 227/32 by stereospecific synthesis
• CPC Class Codes: C07C 229/36 with at least one amino group and one carboxyl group bound to the same carbon atom of the carbon skeleton
• CPC Class Codes: C07C 269/06 by reactions not involving the formation of carbamate groups
• CPC Class Codes: C07C 271/22 to carbon atoms of hydrocarbon radicals substituted by carboxyl groups

Abstract

The invention relates to a method for preparing F-Dopa and ¹⁸F-Dopa and intermediates that are useful in the method. The invention is a method that synthesizes F-Dopa and ¹⁸F-Dopa in good yield with high enantiopurity without the need for further transformations. The method includes the step of reacting a benzaldehyde derivative with a phosphonic acid derivative to produces an olefin intermediate that can be asymmetrically hydrogenated to produce the desired enantiomer.

Claims

1. A compound having the following formula:

wherein R is a methyl group;

R₁ is methoxy;

R₂ is selected from the group consisting of an alkyl having 1 to 4 carbon atoms, and benzyl;

Y is selected from the group consisting of t-butyloxycarbonyl, formyl, acetyl and benzoyl; and

X is a halogen.

2. The compound according to claim 1, wherein X is selected from the group consisting of fluorine, bromine, chlorine, and iodine.

3. The compound according to claim 1, wherein X is fluorine.

4. The compound according to claim 1, wherein R₂ is alkyl having from 1 to 4 carbon atoms.

5. The compound according to claim 1, wherein Y is t-butyloxycarbonyl.

6. The compound according to claim 1, wherein the compound is -2-tert-butoxycarbonylamino-3-(2-fluoro-4,5-dimethoxy-phenyl)-acrylic acid ethyl ester.