Potassium bisulfate → HCID 54497417, compound

Participants

Reaction Conditions

Reaction Steps

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).

Provenance & Evidence