Hydrochloric Acid → Sodium 2-(6-methoxynaphthalen-2-yl)propanoate

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Reaction Steps

Using 6-methoxy-2-vinylnaphthalene formed per (K) above, such as in (c) of the general procedure thereof, charge the following ingredients to a suitable reactor such as a 2-L Hastalloy C Parr reactor: 6-methoxy-2-vinylnaphthalene (MVN), PdCl2, CuCl2, tetrahydrofuran, aqueous HCl, and neomenthyldiphenylphosphine. Seal the reactor and purge several times with carbon monoxide. Then fill the reactor with carbon monoxide and apply heat to the reactor contents. Keep the temperature at about 90° C. while stirring the reaction mixture until completion of the reaction. Recover the (±)-2-(6-methoxy-2-naphthyl)propionic acid from the reaction mixture as sodium (±)-2-(6-methoxy-2-naphthyl)propionate by adding water, toluene and excess aqueous caustic (e.g., 5 to 20% excess as a 20-25% solution) to the reaction mixture, stirring the resultant mixture, and then separating the organic layer from the aqueous phase containing sodium (±)-2-(6-methoxy-2-naphthyl)propionate. Additional workup procedures can be employed to increase the yield and purity of recovered sodium (±)-2-(6-methoxy-2-naphthyl)propionate. This typically involves washing the aqueous phase several times with toluene or like solvent to extract neutral organics remaining therein. Acidification of the sodium (±)-2-(6-methoxy-2-naphthyl)propionate yields (±)-2-(6-methoxy-2-naphthyl)propionic acid. One preferred way of carrying out the acidification involves adding toluene to the toluene-washed aqueous phase, warming to about 80° C., and acidifying with aqueous sulfuric acid. The (±)-2-(6-methoxy-2-naphthyl)propionic acid is isolated by allowing the hot toluene solution to cool to room temperature to crystallize the dissolved (±)-2-(6-methoxy-2-naphthyl)propionic acid. The (±)-2-(6-methoxy-2-naphthyl)propionic acid crystals are collected, rinsed with toluene, rinsed with heptane or pentane to facilitate drying, and brought to constant weight in a vacuum oven operated for example at 52° C. and 2 mm Hg.

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