Hydrochloric Acid → 2-(2,3-Dihydro-1-benzofuran-3-yl)acetic acid

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Reaction Steps

To a solution of methyl [2,3-Dihydro-Benzofuran-3-yl]-acetate (reference example 10b, 6.18 g, 32 mmol) in THF (40 mL), methanol (40 mL) is added a solution of NaOH (40 mL, 1 M). The resulting solution is stirred for 2 hr then acidified with HCl (25 mL, 2M), diluted with ether, washed with brine, dried over MgSO4 and concentrated. The residue crystallized on standing to give the title compound (5.62 g) as a colorless solid. 1H NMR (CDCl3) d 2.69 (dd, J=16, 9 Hz, 1H), 2.89 (dd, J=16, 6 Hz, 1H), 3.88 (m, 1H), 4.30 (dd, J=8, 6 Hz, 1H), 4.77 (t, J=8 Hz, 1H), 6.86 (m, 2H), 7.18 (m, 2H). The racemic acid, prepared above, can be resolved into individual enantiomers by recrystallization of the salt of racemic 3-(carboxy-methyl)-2,3-dihydro-benzofuran (1 eq) with enantiomerically pure a-methylbenzyl amine (0.5 eq) from isopropanol. The free acid is generated from the salt by dissolving the salt in excess aq. HCl (1 M) and extracting the acid into ether. The ether extract is dried over MgSO4 and concentrated to give the enantiomerically pure title compound ad (CH2Cl2, C=10 mg/mL)=−8.4 (using D-(+) a-methyl benzyl amine.

Provenance & Evidence