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

Temperature

130 °C

Prepare the title compound by essentially following procedures as found in Aparajithan, K.; Thompson, A. C.; Sam, J. J. Heterocyclic. Chem. 1966, 3, 466. Dissolve 4,5-dihydro-cyclopenta[b]thiophen-6-one (Bonini, B. F.; et. al. Eur. J. Org. Chem. 2004, 4442 and references cited therein) (0.658 g, 4.77 mmol) in MeOH (50 mL), and add hydroxylamine hydrochloride (0.365 g, 5.25 mmol) and NaOAc (2.35 g, 28.62 mmol). Stir the reaction at RT overnight. Remove the organic solvent in vacuo, and treat the residue with EtOAc (60 mL). Filter through silica gel, wash with EtOAc, and concentrate. Treat the residue with PPA (30 g), heating to 130° C. in an oil bath and with occasional stirring over 30 min. Allow the reaction to cool to RT and pour into ice water (100 mL). Extract with CH2Cl2 (3×150 mL). Wash the combined organic layers with 0.1 M NaOH (100 mL), dry over Na2SO4 and concentrate. Purify the material by chromatography, eluting with 75% EtOAc/hexanes to give 0.521 g (71%) of the title compound. MS/ES m/z 154.1 [M+H]+.

1. customthe reaction at RT overnight
2. customRemove the organic solvent in vacuo
3. additiontreat the residue with EtOAc (60 mL)
4. filtrationFilter through silica gel
5. washwash with EtOAc
6. concentrationconcentrate
7. additionTreat the residue with PPA (30 g)
8. stirringwith occasional stirring over 30 min
9. customthe reaction
10. temperatureto cool to RT
11. extractionExtract with CH2Cl2 (3×150 mL)
12. washWash the combined organic layers with 0.1 M NaOH (100 mL)
13. dry with materialdry over Na2SO4
14. concentrationconcentrate
15. customPurify the material by chromatography
16. washeluting with 75% EtOAc/hexanes

ORD record

ord-1fdb46f8f8d94d8faba81b32c68ac552

Source dataset

uspto-grants-2012_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08101764B2