Pyridine → 5-Chloro-2-(chloromethyl)-2,3-dihydro-1-benzofuran

Temperature

80 °C

To a solution of (5-chloro-2,3-dihydro-1-benzofuran-2-yl)methanol (3 g, 16 mmol) in benzene (50 ml) was added pyridine (1.55 g, 19.6 mmol, 1.2 eq) and thionyl chloride (2.72 g, 23.0 mmol) dropwise with stirring at 0° C. for 7 hours at 80° C. in an oil bath. The reaction mixture was adjusted to ˜pH 8 with aqueous sodium bicarbonate and then extracted with ethyl acetate (3×50 mL). The organic layers were combined, dried over anhydrous magnesium sulfate, filtered, and concentrated under vacuum. The crude material was purified by silica gel chromatography using 3% ethyl acetate in petroleum ether to elute. The product-containing fractions were combined and concentrated under vacuum to afford 5-chloro-2-(chloromethyl)-2,3-dihydro-1-benzofuran as an off-white solid (1.5 g, 46%); 1H NMR (300 MHz, CDCl3): δ 7.06-7.14 (m, 2H), 6.70 (d, J=8.4 Hz, 1H), 4.99-5.10 (m, 1H), 3.64-3.76 (m, 2H), 3.32-3.40 (dd, J=9.3 Hz, 16.2 Hz, 1H), 3.09-3.17 (dd, J=6.6 Hz, 16.2 Hz. 1H).

1. extractionextracted with ethyl acetate (3×50 mL)
2. dry with materialdried over anhydrous magnesium sulfate
3. filtrationfiltered
4. concentrationconcentrated under vacuum
5. customThe crude material was purified by silica gel chromatography
6. washto elute
7. concentrationconcentrated under vacuum

ORD record

ord-0db6b16afde74387b1fe3ed715bc22a5

Source dataset

uspto-grants-2016_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09249102B2