Selective synthesis of racemic 1-11C-labelled norepinephrine, octopamine, norphenylephrine and phenylethanolamine...

A new and simple method for the selective condensation of no-carrier-added [11C]nitromethane (1) with various substituted (protected) benzaldehydes to [beta-11C]beta-nitrophenethyl alcohols was developed. This method which utilizes tetrabutylammonium fluoride in THF as a catalyst gave a condensation yield of 80-90% and a selectivity of 80-90% for [11C]nitroalcohol vs [11C]nitrostyrene formation within 2 min. Reduction of these [11C]nitroalcohols with Raney nickel in formic acid gave the corresponding [11C]aminoalcohols in a yield of 60-90%. Boron tribromide was used for the cleavage of 4-methoxy and 3,4-(methylenedioxy) phenol protecting groups. After HPLC-purification, racemic 1-11C-labelled norepinephrine (7), phenylethanolamine (4), norphenylephrine (5) and octopamine (6) were prepared in a 12-30% decay corrected total radiochemical yield (20-50% counted from 1) with an overall synthesis time of 40-70 min from end of bombardment (EOB). The radiochemical purity was > 98% and the specific radioactivity 700-1500 Ci/mmol (26-56 GBq/mumol).