Tetrabutylammonium borohydride → HCID 58266318, compound

To a solution of (5-bromothiophen-3-yl)-piperidin-1-yl-methanone (907 mg, 3.30 mmol) in DCM (33 mL) was added tetrabutylammonium borohydride (2.54 g, 9.90 mmol) portionwise over 10 minutes. The reaction mixture was heated under reflux for 19 h then further tetrabutylammonium borohydride (2.54 mg, 9.90 mmol) was added to the reaction mixture, in four portions over 6 h. and then the reaction mixture was heated under reflux for 18 h. After this time the reaction mixture was partitioned between DCM (100 mL) and saturated aqueous sodium bicarbonate solution (100 mL). The organic layer was dried over sodium sulfate, the solvent was removed in vacuo and the residue was purified by flash chromatography (silica, 40 g column, ISCO, 0-50% ethyl acetate in cyclohexane) to afford an oil which solidified on standing to afford the title compound as a white solid (301 mg, 35%). 1H NMR (CDCl3, 300 MHz):7.23 (d, J=1.7 Hz, 1H), 7.15 (d, J=1.7 Hz, 1H), 3.91 (s, 2H), 2.97-2.87 (m, 2H), 2.72-2.62 (m, 2H), 2.15-2.06 (m, 2H), 1.70-1.52 (m, 2H), 1.41-1.25 (m, 2H); LCMS (Method B): RT=4.0 min, M+H+=260.

1. temperatureThe reaction mixture was heated
2. temperatureunder reflux for 19 h
3. temperaturethe reaction mixture was heated
4. temperatureunder reflux for 18 h
5. customAfter this time the reaction mixture was partitioned between DCM (100 mL) and saturated aqueous sodium bicarbonate solution (100 mL)
6. dry with materialThe organic layer was dried over sodium sulfate
7. customthe solvent was removed in vacuo
8. customthe residue was purified by flash chromatography (silica, 40 g column, ISCO, 0-50% ethyl acetate in cyclohexane)
9. customto afford an oil which

ORD record

ord-3fbf0406f6174b9aa0aa018548a95fde

Source dataset

uspto-grants-2015_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09216980B2