2-Amino-3-(ethoxycarbonyl)-4-phenylthiophene

Yellow solid

General procedure: A mixture of cyclohexanone (1.06 mL, 10 mmol), ethyl cyanoacetate (1.15 mL, 10 mmol), morpholine (0.90 mL, 10 mmol), sulphur (0.32 g, 10 mmol) in ethanol (10 mL) was stirred and refluxed for overnight. After completion of the reaction, the reaction mixture was cooled to room temperature and the solvent was removed under vacuum. The crude solid was washed with cold ethanol and filtered though sintered funnel, dried under vacuum. The crude product was dissolved in dichloromethane and washed with brine. The organic layer was collected and concentrated under low vacuum to give the compound 2a; yield: 73percent (1.83 g);General procedure: A mixtureof the respective aldehyde or ketone (1 eq), ethylcyanoacetate (1 eq), S8 (1.1 eq), and morpholine(1.5 eq) in EtOH (5 mL) was irradiated at 120 °C for 20 min under microwave conditions. Thereaction mixture was cooled and the solution was poured onto 20 mL ice water to yield a precipitatewhich was filtered, washed with water and dried under vacuum. The crude solid was recrystallizedfrom ethanol to yield the desired product. If the solid was not precipitated from water, extract theaqueous solution with EtOAc (2 x 15 mL) and the organic solution was washed with brine, driedover sodium sulfate and filtered. The solvent was evaporated in vacuo and recrystallized fromappropriate solvent.Sulfur [(126.] 53 mmol) was added to a mixture of crude product 4 (57.5 mmol) and morpholine (66. [1] mmol) in ethanol (150ml) under nitrogen atmosphere. The resulting suspension was stirred at reflux for 14h. After cooling to room temperature, the reaction mixture was concentrated in vacuum. Water was added to the residue, and the product was extracted with ethyl acetate (3 x [1 00ML).] The combined organic layer was dried over sodium sulfate and concentrated. A [2-AMINO-4-ARYL-5-ALKYL-THIOPHENE-3-CARBOXYLIC] acid ethyl ester 5 (shown below) was purified by column chromatography (Hexanes: Ethyl acetate 10: 4). Typical yields were 50-70percent.2-Cyano-3-phenyl-but-2-enoic acid ethyl ester (513.25 g, 2.3 mol) was added at ambient temperature to a vigorously-stirred suspension of powdered sulfur (76 g, 2.3 mol) in ethanol (500 ml). Part B:

ethyl-2-amino-4-phenyl-Thiophene-3-carboxylate is a synthetic intermediate useful for pharmaceutical synthesis.

Molecular Weight:247.31
XLogP3:3.7
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:4
Rotatable Bond Count:4
Exact Mass:247.06669983
Monoisotopic Mass:247.06669983
Topological Polar Surface Area:80.6
Heavy Atom Count:17
Complexity:266
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes