4H,5H,6H-cyclopenta(b)thiophen-6-one → 5,6-Dihydrothieno[2,3-c]pyridin-7(4H)-one

Temperature

130 °C

A solution of 4H-cyclopenta[b]thiophen-6(5H)-one (1.34 g, 9.7 mmol), hydroxylamine HCl (1.45 g, 20.8 mmol) and NaOAc (7.3 g, 89.0 mmol) in MeOH (150 mL) was stirred overnight at room temperature. The reaction was then concentrated under reduced pressure, taken up in EtOAc (100 mL) and filtered over a plug of silica gel, eluting with EtOAc. The filtrate was concentrated, taken up in polyphosphoric acid (100 g) and heated for 2 h at 130° C. Upon completion, the reaction was quenched by pouring over ice water (100 mL). The aqueous mixture was extracted with DCM (2×100 mL) and the combined extracts were washed with 0.1 M NaOH (100 mL), dried over Na2SO4, then filtered and concentrated. 5,6-dihydrothieno[2,3-c]pyridin-7(4H)-one (837 mg, 55% yield) was isolated as a white solid after purification by flash chromatography over silica gel (20-30% EtOAc/hexane eluent). 1H NMR (300 MHz, MeOH) δ ppm 7.69 (d, J=5.0 Hz, 1H), 7.06 (d, J=5.0 Hz, 1H), 3.57 (t, J=7.1 Hz, 2 H), 2.94 (t, J=7.1 Hz, 2H); MS (EI) m/z=154.2 [M+1]+.

1. concentrationThe reaction was then concentrated under reduced pressure
2. filtrationfiltered over a plug of silica gel
3. washeluting with EtOAc
4. concentrationThe filtrate was concentrated
5. customUpon completion, the reaction was quenched
6. additionby pouring over ice water (100 mL)
7. extractionThe aqueous mixture was extracted with DCM (2×100 mL)
8. washthe combined extracts were washed with 0.1 M NaOH (100 mL)
9. dry with materialdried over Na2SO4
10. filtrationfiltered
11. concentrationconcentrated

ORD record

ord-e752963553b648b88aa59f26a7d52526

Source dataset

uspto-grants-2013_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08440652B2