Sodium hydride → 8-chloro-5-methyl-5H-chromeno[3,4-c]pyridine

To a stirred suspension of NaH (3.81 mg, 0.159 mmol) in anhydrous THF (5 mL), was added a THF (5 mL) solution of 1-(4-(4-chloro-2-fluorophenyl)pyridin-3-yl)ethanol (20 mg, 0.079 mmol) dropwise and the reaction mixture was stirred at room temperature for 4 h. The reaction was quenched by addition of saturated aqueous ammonium chloride solution (15 mL) and the product was extracted with ethyl acetate (3×20 mL). The combined organics were washed with water (1×15 mL) and brine (1×15 mL), dried over sodium sulfate and concentrated under reduced pressure. The residue was purified via preparative TLC (40% ethyl acetate in hexane) to afford 8-chloro-5-methyl-5H-chromeno[3,4-c]pyridine (12 mg, 0.052 mmol, 63% yield). 1H NMR (400 MHz, CDCl3) δ 8.59 (d, J=5.2 Hz, 1H), 8.42 (s, 1H), 7.66 (d, J=8.3 Hz, 1H), 7.49 (d, J=5.2 Hz, 1H), 7.06 (m, 2H), 5.36 (q, J=6.6 Hz, 1H), 1.66 (d, J=6.6 Hz, 3H); LCMS (ESI) m/e 232 [(M+H)+, calcd for C13H11ClNO 232.1].

1. customThe reaction was quenched by addition of saturated aqueous ammonium chloride solution (15 mL)
2. extractionthe product was extracted with ethyl acetate (3×20 mL)
3. washThe combined organics were washed with water (1×15 mL) and brine (1×15 mL)
4. dry with materialdried over sodium sulfate
5. concentrationconcentrated under reduced pressure
6. customThe residue was purified via preparative TLC (40% ethyl acetate in hexane)

ORD record

ord-c482ddbb50aa49c2b71a09a1f610bc59

Source dataset

uspto-grants-2015_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08969564B2