Tetrahydrofuran → 2-(Isochroman-1-yl)-2-methylpropionic acid

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Reaction Steps

Sodium hydroxide (1N, 12 ml) is added dropwise over several minutes, followed by a few mls of THF (to aid in solution) to a mixture of methyl 2-(isochroman-1-yl)-2-methylpropionate (LXXI, 1.833 g, 7.8 mmol) in ethanol (12 ml). The mixture is stirred overnight at 20°-25°, then at 47° for 2 hr, followed by stirring at 20°-25° over the weekend. Additional THF and sodium hydroxide (1N, 12 ml) are added and the mixture is stirred overnight at 20°-25° and then at 40° for 7 hr, followed by overnight at 20°-25°. Ethanol is then removed under reduced pressure and the resulting solids are dissolved in water. The aqueous phase is separated and washed twice with hexane to remove any unreacted starting material and the aqueous phase is then cooled in an ice/water bath and hydrochloric acid (4N, 6 ml) is added dropwise. The mixture is extracted three times with ether and the combined organic phases are backwashed with saline, dried over magnesium sulfate, and concentrated. Recrystallization from dichloromethane/hexane gives 2-(isochroman-1-yl)-2-methylpropionic acid (LXXII), mp 110.5°-115.75°.

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