Pyridine → 7-Bromo-3,3-dimethyl-2,3-dihydro-benzofuran-5-carboxylic acid methylamide

To a solution of 7-bromo-3,3-dimethyl-2,3-dihydro-benzofuran-5-carboxylic acid (4.99 g, 18.41 mmol) in dry THF (40 mL) was added at room temperature thionychloride (2 mL, 27.61 mmol) and DMF (0.14 mL, 1.84 mmol). The reaction mixture was stirred 1 hr then methylamine hydrochloride (2.48 g, 36.82 mmol) was added followed by slow addition of pyridine (4.5 mL, 55.23 mmol). The reaction mixture was stirred overnight then water and ethyl acetate were added. The layers were separated. The aqueous layer was extracted twice with ethyl acetate. The combined extracts were washed successively with water and brine, dried over anhydrous magnesium sulfate, filtered and evaporated. The residue was chromatographed on silica gel (50% to 100% ethyl acetate in hexane, then 40% MeOH in Ethyl acetate) to give 1.17 g of 7-bromo-3,3-dimethyl-2,3-dihydro-benzofuran-5-carboxylic acid methylamide (22%). 1H NMR (300 MHz; CDCl3): 1.36 (s, 6H), 2.99 (d, J=4.5 Hz, 3H), 4.39 (s, 2H), 6.25 (br s, 1H), 7.54 (d, J=1.5 Hz, 1H), 7.70 (d, J=1.5 Hz, 1H).

1. stirringThe reaction mixture was stirred overnight
2. customThe layers were separated
3. extractionThe aqueous layer was extracted twice with ethyl acetate
4. washThe combined extracts were washed successively with water and brine
5. dry with materialdried over anhydrous magnesium sulfate
6. filtrationfiltered
7. customevaporated
8. customThe residue was chromatographed on silica gel (50% to 100% ethyl acetate in hexane

ORD record

ord-996cdac4254441578be78053e653fca3

Source dataset

uspto-grants-2007_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07196108B2