Patent ID: 7138540

Claim:
A method of producing a precursor of 18 F-labeled O-(2-[ 18 F]fluoroethyl)-L-Tyrosine, which has the following chemical structure: wherein R 1 is a protective group for the carboxyl functional group and represents an arylalkyl group; R 2 is a protective group for the amino group and represents a carboxyl group; and R 3 acts as a leaving group and represents a p-tosyloxy, methane sulfonyloxy or trifluoromethane sulfonyloxy or bromine, said method comprising step (a) preparation of ethylene glycol-1,2-ditosylate and step (b) preparation of t-BOC-(O-tosyloxyethyl)-L-TYr-OBzl, wherein step (a) comprises: (1) adding toluenesulfonyl chloride (TsCl) to pyridine to form a first solution; (2) adding ethylene glycol to pyridine to form a second solution, (3) pouring the first solution into the second solution under the temperature of dry ice-acetone bath (−30° C. approximately) to form a mixture and then keeping the mixture under −18° C. promptly for reacting two to three days; (4) pouring the mixture from (3) into ice water and cracked ice; then stirring until a white solid substance appears; (5) adding optimal 1N HCl into the white solid substance and adjusting the pH of the resultant solution to 6˜7; and (6) filtering and collecting the white solid substance then re-crystallizing the white solid substance in a mixture of methylene chloride and normal hexane to yield ethylene glycol-1,2-ditosylate, and step (b) comprises: (1) adding N-tert-butyloxycarbonyl-L-tyrosine benzylester (t-BOC-L-Tyr-OBzl) to a mixture of potassium carbonate and ethylene glycol-1,2-ditosylate; then adding anhydrous acetonitrile at 90° C. and stirring the resultant mixture for 3.5 hours, (2) removing the solvent from the mixture from (1) with rotavapor and extracting it with chloroform (5 ml x3); harvesting the chloroform extract and removing the solvent under negative pressure to yield a solid residue; (3) dissolving the solid residue with methylene chloride then performing silica gel chromatography (with addition of 0.1% triethylamine in eluent) for purification, wherein the initial condition of mobile phase is 100% CH 2 Cl 2 and after removing unreacted ethylene glycol-1,2-ditosylate the condition of mobile phase is changed to CH 2 Cl 2 /CHCl 3 =1/1, a crude product being eluted; (4) drying the crude product under reduced pressure to obtain a solid crude product; (5) dissolving the solid crude product with a minimum volume of solution CH 2 Cl 2 :CHCl 3 =8/2, then performing silica gel chromatography (with addition of 0.1% triethylamine in eluent) for purification, wherein the initial condition of mobile phase is CH 2 Cl 2 /CHCl 3 =8/2, (with another addition of 0.1% triethylamine) a light yellow oil-like substance of pure N-tert-butyloxycarbonyl-(O-tosyloxyethyl)-L-tyrosine benzylester (t-BOC-(O-tosyloxyethyl)-L-Tyr-OBzl) being eluted; and (6) re-crystallizing the product from (5) in dichloromethane and n-hexane to yield a white solid substance.