Cesium carbonate → 2-Cyclopropyl-4H-thieno[2,3-c]pyrrol-6(5H)-one

Temperature

100 °C

A 100-mL single-neck round-bottomed flask equipped with a reflux condenser, magnetic stirrer and nitrogen inlet was charged with 116f (900 mg, 4.12 mmol), potassium cyclopropyltrifluoroborate (733 mg, 4.95 mmol), cesium carbonate (4.03 g, 12.4 mmol), toluene (18 mL), water (1 mL). After bubbling nitrogen through the resulting suspension for 30 min, palladium(II) acetate (279 mg, 0.412 mmol) and n-butyldi-1-adamantylphosphine (222 mg, 0.618 mmol) were added, and the reaction mixture was heated at 100° C. for 14 h. After this time, the mixture was cooled to room temperature and diluted with ethyl acetate (150 mL) and water (30 mL). The organic layer was separated, and the aqueous layer was extracted with ethyl acetate (3×150 mL). The combined organic layers were dried over sodium sulfate and concentrated under reduced pressure. The residue was purified by column chromatography (silica, 0% to 5% methanol/methylene chloride) to afford a 35% yield (254 mg) of 116g as an off-white solid: mp 109-110° C.; 1H NMR (300 MHz, CDCl3) δ 6.72 (s, 1H), 6.08 (br s, 1H), 4.28 (s, 2H), 2.16 (m, 1H), 1.09 (m, 2H), 0.84 (m, 1H); MS (ESI+) m/z 180.1 (M+H).

1. customA 100-mL single-neck round-bottomed flask equipped with a reflux condenser, magnetic stirrer and nitrogen inlet
2. customAfter bubbling nitrogen through the resulting suspension for 30 min
3. temperatureAfter this time, the mixture was cooled to room temperature
4. customThe organic layer was separated
5. extractionthe aqueous layer was extracted with ethyl acetate (3×150 mL)
6. dry with materialThe combined organic layers were dried over sodium sulfate
7. concentrationconcentrated under reduced pressure
8. customThe residue was purified by column chromatography (silica, 0% to 5% methanol/methylene chloride)

ORD record

ord-d5627244e64343129f2a8ecf76f25659

Source dataset

uspto-grants-2016_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09249123B2