Ethyl 4-bromobutyrate → (9S)-4-[9-Hydroxycinchonan-6'-yl)oxybutanoic acid

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Reaction Steps

The first step in the synthesis of the tracer of the present invention, as for the hapten, is the alkylation of 6-hydroxyquinidine using preferably one or less molar equivalent of alkylating reagent. The first step is the alkylation of 6-hydroxyquinidine(1) to (9S)-4-[(9-Hydroxycinchonan-6'-yl) oxybutanoic acid ethyl ester (5) using one molar equivalent of ethyl 4-bromobutyrate, most preferably using 0.9 molar equivalent of ethyl 4-bromobutyrate. The alkylated product (5) is hydrolyzed to obtain the corresponding acid (9S)-4-[9-Hydroxycinchonan-6'-yl)oxybutanoic acid (6). The acid is activated to form N-hydroxysuccinimide using a method well-known in the literature. This activated ester is coupled with 5-aminomethylfluorescein in the presence of pyridine to give the quinidine tracer (9S)-N-[(3',6'-dihydroxy-3-oxospiro[isobenzofuran-1(3H),9'-[9H]xanthen]-5yl) methyl]-4-[(9-hydroxycinchonan-6'-yl)oxy]butamide (7).

Provenance & Evidence