Cesium carbonate → Methyl 4-fluorothieno[2,3-c]pyridine-2-carboxylate

Temperature

0 °C

To a cooled (0° C.) solution of 3,5-difluoro-4-formylpyridine (1.00 g, 6.99 mmol) in THF (12.3 mL) was added mercaptoacetic acid methyl ester (625 μL, 6.99 mmol). The reaction stirred 1 h at 0° C. and 1 h at room temperature, and then cesium carbonate (2.28 g, 6.99 mmol) was added. The reaction then stirred a further 18 h at room temperature. The reaction mixture was then partitioned between ethyl acetate (50 mL) and brine (50 mL). The layers were separated and the organic fraction was washed with water (1×50 mL) and brine (1×25 mL), then dried over sodium sulfate, filtered, and concentrated. Purification by ISCO chromatography (20 to 40% ethyl acetate:hexanes) afforded 942 mg (64%) of the title compound as a white solid. 1H NMR (400 MHz, DMSO-d6): δ 9.23-9.29 (m, 1 H), 8.56 (dd, J=2.0, 0.5 Hz, 1 H), 8.25 (d, J=0.8 Hz, 1 H), 3.94 (s, 3 H); MS (ESI): 212.09 [M+H]+; HPLC tR=3.17 min (ZQ3, polar—4 min).

1. customThe reaction
2. stirringthen stirred a further 18 h at room temperature
3. customThe reaction mixture was then partitioned between ethyl acetate (50 mL) and brine (50 mL)
4. customThe layers were separated
5. washthe organic fraction was washed with water (1×50 mL) and brine (1×25 mL)
6. dry with materialdried over sodium sulfate
7. filtrationfiltered
8. concentrationconcentrated
9. customPurification by ISCO chromatography (20 to 40% ethyl acetate:hexanes)

ORD record

ord-110ba79a8fb04365ab7031c2a5eccbeb

Source dataset

uspto-grants-2013_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08378104B2