Hydrochloric Acid → 5-Chloro-2,3-dihydro-benzofuran-2-carboxylic acid

Temperature

0 °C

To a solution of (5-chloro-2,3-dihydro-1-benzofuran-2-yl)methanol (2 g, 11 mmol), KHCO3 (4.32 g, 43 mmol, 4 eq) and TEMPO (20 mg, 0.13 mmol, 0.1 eq) in water (8 ml) and CH3CN (18 ml) was added NaOCl (20 ml, aq. 15%, ˜4 eq) dropwise with stirring at 0° C. and stirred for 1 hour. The mixture was diluted with water (200 ml) and adjusted to pH˜4 with hydrogen chloride (2N). After extraction with ethyl acetate (3×200 ml), the organic layers were combined, washed with brine (200 ml), dried over anhydrous sodium sulfate, filtered, and then concentrated under vacuum. The crude material was purified by silica gel chromatography using 1% methanol in dichloromethane to elute. The product-containing fractions were combined and concentrated under vacuum to afford 5-chloro-2,3-dihydro-1-benzofuran-2-carboxylic acid as a yellow solid (1.6 g, 74%). 1H NMR (300 MHz, CDCl3): δ 7.05-7.22 (m, 2H), 6.83 (d, J=8.4 Hz, 1H), 5.20-5.30 (m, 1H), 3.56-3.65 (m, 1H), 3.33-3.45 (m, 1H)

1. stirringstirred for 1 hour
2. extractionAfter extraction with ethyl acetate (3×200 ml)
3. washwashed with brine (200 ml)
4. dry with materialdried over anhydrous sodium sulfate
5. filtrationfiltered
6. concentrationconcentrated under vacuum
7. customThe crude material was purified by silica gel chromatography
8. washto elute
9. concentrationconcentrated under vacuum

ORD record

ord-4261c767237b48f5ac308dfc6d4530e7

Source dataset

uspto-grants-2016_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09249102B2