Hydrochloric Acid → 4,5,6,7-Tetrahydrothieno(3,2-c)pyridine

Under ice-cooling, 10% sodium hydroxide aqueous solution (10 ml) was added dropwise to ethanol solution (200 ml) of 3-thiophene aldehyde (11 g, 98 mmol) and nitromethane (6.0 g, 98 mmol). After the dropwise addition, the reaction solution was added dropwise to 5 N hydrochloric acid, and the thus formed precipitate was collected by filtration, washed with water and then dried to obtain crude 2-(3-thieno)-1-nitroethylene as yellow powder (yield, 10 g). At room temperature, diethyl ether solution (60 ml) of the crude 2-(3-thieno)-1-nitroethylene (1.55 g, 10 mmol) was added dropwise to diethyl ether suspension (20 ml) of lithium aluminum hydride (760 mg, 20 mmol), spending 40 minutes, and then the mixture was stirred for 20 minutes. Cold water was added to the reaction solution in small portions, and celite filtration was carried out when precipitate was formed. The precipitate was washed with ethyl acetate, combined with the filtrate, washed with saturated brine and dried with anhydrous magnesium sulfate, and then the solvent was removed by evaporation under a reduced pressure. The residue was mixed with water (1.1 ml) and 37% formaldehyde aqueous solution (620 mg, 10 mmol) and vigorously stirred at 100° C. for 3 hours. The solvent was removed by evaporation from the reaction solution under a reduced pressure, and the thus obtained residue was mixed with 5 N hydrochloric acid (2.2 ml) and concentrated hydrochloric acid (0.22 ml) and vigorously stirred at room temperature for 3 hours. The reaction solution was alkalified by adding sodium hydroxide aqueous solution, and the reaction product was extracted therefrom with ethyl acetate, washed with saturated brine and dried using anhydrous magnesium sulfate. The solvent was removed by evaporation from the organic layer under a reduced pressure, and the thus obtained material was separated and purified by a silica gel column chromatography to obtain 310 mg (2.2 mmol, 22% in yield) of the title compound.

1. temperatureUnder ice-cooling
2. additionAfter the dropwise addition
3. filtrationthe thus formed precipitate was collected by filtration
4. washwashed with water
5. customdried
6. customto obtain
7. customcrude 2-(3-thieno)-1-nitroethylene as yellow powder (yield, 10 g)
8. customwas formed
9. washThe precipitate was washed with ethyl acetate
10. washwashed with saturated brine
11. dry with materialdried with anhydrous magnesium sulfate
12. customthe solvent was removed by evaporation under a reduced pressure
13. stirringvigorously stirred at 100° C. for 3 hours
14. customThe solvent was removed by evaporation from the reaction solution under a reduced pressure
15. additionthe thus obtained residue was mixed with 5 N hydrochloric acid (2.2 ml) and concentrated hydrochloric acid (0.22 ml)
16. stirringvigorously stirred at room temperature for 3 hours
17. additionby adding sodium hydroxide aqueous solution
18. extractionthe reaction product was extracted
19. washwith ethyl acetate, washed with saturated brine
20. customdried
21. customThe solvent was removed by evaporation from the organic layer under a reduced pressure
22. customthe thus obtained material was separated
23. custompurified by a silica gel column chromatography
24. customto obtain

ORD record

ord-7dd84e507d8f4a15b6b3625ef060c0c4

Source dataset

uspto-grants-2002_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06498251B1