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

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.

1. washwashed with brine
2. dry with materialdried over MgSO4
3. concentrationconcentrated
4. customThe residue crystallized

ORD record

ord-c359c41479044aa89d3df71a7079f6c0

Source dataset

uspto-grants-2003_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06599918B2