Reaction #1178430

Reaction equation

1-hydroxybenzotriazole hydrate

5-chlorothiophenecarboxylic acid

N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride

N-methylmorpholine

N-[4-(3-oxomorpholin-4-yl)phenyl]pyrrolidine-2-carboxamide

→

N-[4-(3-oxomorpholin-4-yl)phenyl]-(R)-1-(5-chlorothiophene-2-carbonyl)-pyrrolidine-2-carboxamide

Solvents

dimethylformamide

Conditions

Workup

1. 1
   OtherThe solution is subsequently evaporated to dryness under reduced pressure
2. 2
   Extractionthe sodium hydrogencarbonate solution is extracted twice with 10 ml of ethyl acetate each time
3. 3
   DryingAfter the combined organic phases have been dried over sodium sulfate
4. 4
   Otherthe solid residue is triturated with 20 ml of diethyl ether
5. 5
   Othergiving 1.2 g (59.4%) of “AB1”, ESI 434

Procedure

0.71 g (4.66 mmol) of 1-hydroxybenzotriazole hydrate, 0.76 g (4.66 mmol) of 5-chlorothiophenecarboxylic acid, 1.79 g (9.33 mmol) of N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (DAPECI) and 1.13 ml of N-methylmorpholine are added successively to a solution of 1.35 g (4.66 mmol) of N-[4-(3-oxomorpholin-4-yl)phenyl]pyrrolidine-2-carboxamide in 30 ml of dimethylformamide, and the resultant solution is stirred at room temperature for 12 hours. The solution is subsequently evaporated to dryness under reduced pressure, the residue is taken up in 10 ml of 5% sodium hydrogencarbonate solution, and the sodium hydrogencarbonate solution is extracted twice with 10 ml of ethyl acetate each time. After the combined organic phases have been dried over sodium sulfate and the solvent has been stripped off, the solid residue is triturated with 20 ml of diethyl ether, giving 1.2 g (59.4%) of “AB1”, ESI 434; m.p. 195°.

Source