Potassium bisulfate → HCID 54497417, compound

Temperature

20 °C

In an atmosphere of argon gas, potassium (25 g) was added to dried tert-butanol (820 ml) and refluxed for 3 hrs to give a solution. To the solution cooled to 20° C. was added diethyl ether (300 ml) and then slowly added a solution of methyl crotonate (63.93 g) and tert-butyl 5-formyl-2-thiophenecarboxylate (73.1 g) in tert-butanol/diethyl ether (2:1, 300 ml) keeping an inner temperature to 10° C. The mixture was stirred for 2 hrs at the same temperature and adjusted to pH 4 by adding 1N-potassium hydrogen sulfate aqueous solution (750 ml) under cooling. The mixture was extracted with diethyl ether, and the extract was washed with water and then saturated saline solution and distilled under reduced pressure to remove the solvent. The residue was dissolved in ethyl acetate (100 ml), to which 5% Pd-C (15 g:commercially available from Engelhard) was added. The mixture was vigorously stirred for 3 hrs at room temperature under hydrogen pressure of 4 kg/cm2. The reaction mixture was filtered to remove the catalyst and the filtrate was distilled under reduced pressure to remove the solvent. To the resulting residue were added dry methanol (200 ml), 4-(N,N-dimethylamino)pyridine (30 mg) and dichloromethane (250 ml), to which a solution of 1,3-dicyclohexylcarbodiimide (132 g) in dichloromethane (250 ml) was added slowly dropwise at 0° C. The mixture was stirred for 18 hrs at room temperature and cooled to 0° C. After adding acetic acid (30 ml), the mixture was stirred for 30 mins at 0° C. and for 30 mins at room temperature. The resulting precipitate was filtered off and the filtrate was concentrated to dryness under reduced pressure. Ethyl acetate (100 ml) was added to the residue and allowed to stand for 2 hrs at 0° C. Again, the resulting precipitate was filtered off and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography using diethyl ether-hexane=1:15→1:5, to obtain the captioned compound (61.4 g).

1. temperaturerefluxed for 3 hrs
2. customto give a solution
3. customto 10° C
4. temperatureunder cooling
5. extractionThe mixture was extracted with diethyl ether
6. washthe extract was washed with water
7. distillationsaturated saline solution and distilled under reduced pressure
8. customto remove the solvent
9. dissolutionThe residue was dissolved in ethyl acetate (100 ml), to which 5% Pd-C (15 g
10. additioncommercially available from Engelhard) was added
11. stirringThe mixture was vigorously stirred for 3 hrs at room temperature under hydrogen pressure of 4 kg/cm2
12. filtrationThe reaction mixture was filtered
13. customto remove the catalyst
14. distillationthe filtrate was distilled under reduced pressure
15. customto remove the solvent
16. additionTo the resulting residue were added dry methanol (200 ml), 4-(N,N-dimethylamino)pyridine (30 mg) and dichloromethane (250 ml)
17. additionto which a solution of 1,3-dicyclohexylcarbodiimide (132 g) in dichloromethane (250 ml) was added slowly dropwise at 0° C
18. stirringThe mixture was stirred for 18 hrs at room temperature
19. temperaturecooled to 0° C
20. additionAfter adding acetic acid (30 ml)
21. stirringthe mixture was stirred for 30 mins at 0° C. and for 30 mins at room temperature
22. filtrationThe resulting precipitate was filtered off
23. concentrationthe filtrate was concentrated to dryness under reduced pressure
24. additionEthyl acetate (100 ml) was added to the residue
25. waitto stand for 2 hrs at 0° C
26. filtrationAgain, the resulting precipitate was filtered off
27. concentrationthe filtrate was concentrated under reduced pressure
28. customThe residue was purified by silica gel column chromatography

ORD record

ord-b380f23621d44c5aa772860a9d582dcc

Source dataset

uspto-grants-1994_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05354754