Hydrochloric Acid → 7-methoxy-1,2,3,4-tetrahydro-(2R)-2-naphthoic acid

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Reaction Steps

5 g (0.022 mol) of methyl 7-methoxy-1,2,3,4-tetrahydro-2-naphthoate are dissolved in 175 ml of tert-butanol, and 500 ml of phosphate buffer at pH 7 are added to the solution prepared in this way. The pH of the solution, which rises to a value of 7.3-7.5, is lowered to 7.1 by the addition of 1N HCl. 3.5 g of Sigma PPL enzyme (known as porcine pancreatic lipase type II, crude, Sigma L-3126--39 U/mg using triacetin) are added to the mixture. The pH tends to drop as the reaction progresses, but is kept constant by the addition of a 0.25N solution of NaOH. After 6 hours, when about 31.75 ml of 0.25N NaOH have been consumed, sodium bicarbonate is added to the solution until the pH is about 8 in order to stop the reaction by inactivation of the enzyme. Extraction is carried out with ethyl ether and the two phases are separated. The organic phase contains the unreacted ester principally of (S) configuration, which can be recovered as indicated in Example 5. The aqueous phase is acidified with concentrated sulfuric acid and the precipitate formed is filtered off to give 1.25 g of the title acid. [α]D20 =+43.67° (c=1.4%, CHCl3); ee 93.27% (HPLC performed under conditions (a)). This product is equivalent to that described in preparation (G) (i) of EP-A-436435, obtained after 10 crystallizations.

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