Reaction #1178461

Reaction equation

hydrochloric acid

5-chloro-2-thiophenecarboxaldehyde

malonic acid

water

→

(E)-3-(5-chlorothiophen-2-yl)acrylic acid

Yield 81.7%

Solvents

piperidine

pyridine

Conditions

Workup

1. 1
   Temperatureto cool
2. 2
   OtherThe product which precipitates in the process
3. 3
   Filtrationis filtered off with suction
4. 4
   Otherdried in a drying cabinet at 80° C.

Procedure

The solution of 1 g (6.62 mmol) of 5-chloro-2-thiophenecarboxaldehyde and 1.38 g (13.23 mmol) of malonic acid in 0.07 ml of piperidine and 5 ml of pyridine is refluxed for 2 hours. The reaction solution is subsequently allowed to cool, then poured into 20 ml of water and acidified to pH 1 using 2N hydrochloric acid. The product which precipitates in the process is filtered off with suction and dried in a drying cabinet at 80° C., giving 1.02 g of (E)-3-(5-chlorothiophen-2-yl)acrylic acid as brown crystals, ESI 189. Analogously to Example 7.1, reaction between the compound of Example 7.2 and (E)-3-(5-chlorothiophen-2-yl)acrylic acid gives the compound N-[4-(3-oxomorpholin-4-yl)phenyl]-(2R,4R)-1-[(E)-3-(5-chlorothiophen-2-yl)acryloyl]-4-hydroxypyrrolidine-2-carboxamide as colourless crystals, ESI 476, m.p. 151°.

Source