Reaction #531881

Reaction equation

triethylamine

ethyl 3-chloro-3-(3-chloro-4-methyl-2-thienyl)-2-cyanoacrylate

N-methyl-L-alaninamide hydrochloride

→

ethyl (2Z)-3-(3-chloro-4-methyl-2-thienyl)-2-cyano-3-{[(2R)-1-(methylamino)-1-oxopropan-2-yl]amino}acrylate

Yield 60.4%

Solvents

acetonitrile

Conditions

Workup

1. 1
   OtherThe reaction was microwaved
2. 2
   Other(130° C., 300 s, fixed hold, high absorption)
3. 3
   Otherthe solvent evaporated
4. 4
   OtherThe residual oil was triturated in ethyl acetate
5. 5
   Otherthe white solid removed by filtration
6. 6
   ConcentrationAfter concentration under vacuum

Procedure

To a solution of ethyl 3-chloro-3-(3-chloro-4-methyl-2-thienyl)-2-cyanoacrylate (0.351 g, 1.21 mmol, 1 eq.) in 3 ml of acetonitrile was added N-methyl-L-alaninamide hydrochloride (0.201 g, 1.45 mmol, 1.2 eq.) followed by triethylamine (TEA) (0.490 g, 4.84 mmol, 4 eq.). The reaction was microwaved (130° C., 300 s, fixed hold, high absorption) and the solvent evaporated. The residual oil was triturated in ethyl acetate and the white solid removed by filtration. After concentration under vacuum, the residual oil was subjected to column chromatography to give ethyl (2Z)-3-(3-chloro-4-methyl-2-thienyl)-2-cyano-3-{[(2R)-1-(methylamino)-1-oxopropan-2-yl]amino}acrylate (0.26 g, 57% yield) as a mixture of atropoisomers.

Source