Reaction #2467971

Reaction equation

sodium methoxide

methyl thioglycolate

sodium methoxide

3-chloro-3-phenylprop-2-enenitrile

water

→

solid

Yield 62.9%

Methyl 3-amino-5-phenylthiophene-2-carboxylate

Yield 62.9%

Solvents

methanol

methanol

methanol

DMF

Conditions

Workup

1. 1
   workup.STIRRINGstirred the mixture at 60° C. for 2 h
2. 2
   workup.STIRRINGstirring
3. 3
   workup.WAITwas continued for 2 h at 60° C
4. 4
   Otherwas allowed to rt
5. 5
   workup.STIRRINGstirred for 15 min
6. 6
   ExtractionThe solution was extracted with chloroform (3×100 mL)
7. 7
   Washthe combined chloroform layer was washed with water, brine
8. 8
   Dryingdried over sodium sulfate
9. 9
   FiltrationThe solution was filtered
10. 10
    Otherevaporated the solvent
11. 11
    OtherThe residue was chromatographed over silica gel

Procedure

To a solution of methyl thioglycolate (1 g, 9.43 mmol) in methanol (5 mL) was added a solution of sodium methoxide (0.5 g, 9.43 mmol) in methanol (5 mL) and stirred for 0.5 h. To the above mixture, a solution of 3-chloro-3-phenylprop-2-enenitrile (1.22 g, 7.5 mmol) in DMF (3.5 mL) was added dropwise for 10 min at rt and stirred the mixture at 60° C. for 2 h. Then, a solution of sodium methoxide (1 g, 18.6 mmol) in methanol (10 mL) was added dropwise at rt and stirring was continued for 2 h at 60° C. The mixture was allowed to rt and poured into cold water and stirred for 15 min. The solution was extracted with chloroform (3×100 mL) and the combined chloroform layer was washed with water, brine and dried over sodium sulfate. The solution was filtered and evaporated the solvent. The residue was chromatographed over silica gel using hexane-ethyl acetate (92:8) as eluent to give the product as a pale yellow color solid (1.1 g, 50%), mp 130-132° C. 1H NMR (400 MHz, DMSO-d6): δ 7.62-7.65 (2H, m), 7.38-7.48 (3H, m), 7.00 (1H, s), 4.29 (2H, br s), 3.74 (3H, s); LC-MS (positive ion mode): m/z 234 (M+H)+.

Source