Sodium Hydroxide → (6-Bromoisochroman-1-yl)acetic acid

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Reaction Steps

Sodium hydroxide (1N, 19.8 ml) is added to ethyl (6-bromoisochroman-1-yl)acetate (LXXVII, 3.96 g, 13.2 mmol) in ethanol (20 ml). The mixture is stirred for 2 hr, at which time the ethanol is removed under reduced pressure. The residue is acidified with hydrochloric acid (4N, approximately 6 ml) and extracted with ether. The organic phase is separated and is washed with dilute aqueous hydrochloric acid, dilute aqueous hydrochloric acid/saline, and saline, dried over magnesium sulfate, and concentrated under reduced pressure. The (6-bromoisochroman-1-yl)acetic acid (LXVIII) thus obtained is stirred at 0° with THF (20 ml) and borane-methyl sulfide (3.75 ml, 39.6 mmol) is added over several minutes. After stirring at 0° for 3.5 hr, the mixture is allowed to slowly warm to 20-25° and methanol is added to quench excess borane, until no further gas evolution is observed. The mixture is then concentrated under reduced pressure and methanol is again added and removed under reduced pressure. This procedure is repeated twice and the residue is then partitioned between dichloromethane, aqueous sodium bicarbonate and saline. The organic phase is separated, dried over sodium sulfate and concentrated to give 2-(6-bromoisochroman-1-yl)ethanol (LXXIX), NMR (CDCl3) 2.04, 2.21, 2.65, 3.02, 3.70-3.87, 4.17, 4.92, 6.93 and 7.28 δ.

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