Reaction #1178449

Reaction equation

4-chlorophenylacetic acid

ethyl 2-ethoxy-1,2-dihydroquinoline-1-carboxylate

N-[4-(3-oxomorpholin-4-yl)phenyl]-(2R,4R)-4-hydroxypyrrolidine-2-carboxamide

triethylamine

→

N-[4-(3-oxomorpholin-4-yl)phenyl]-(2R,4R)-1-[2-(4-chlorophenyl)acetyl]-4-hydroxypyrrolidine-2-carboxamide

Yield 46.4%

Solvents

toluene

Conditions

Workup

1. 1
   OtherThe resultant reaction mixture
2. 2
   workup.WAITis subsequently left
3. 3
   Washwashed successively with 10 ml of 1N hydrochloric acid and 10 ml of saturated sodium hydrogencarbonate solution
4. 4
   Dryingthe organic phase is dried over sodium sulfate
5. 5
   Otherthe crude product is purified by preparative HPLC

Procedure

0.25 g (1.46 mmol) of 4-chlorophenylacetic acid and 0.36 g (1.46 mmol) of ethyl 2-ethoxy-1,2-dihydroquinoline-1-carboxylate (EEDQ) are added successively at room temperature to a solution of 0.5 g (1.46 mmol) of N-[4-(3-oxomorpholin-4-yl)phenyl]-(2R,4R)-4-hydroxypyrrolidine-2-carboxamide (Example 7.2) and 0.2 ml of triethylamine in 20 ml of toluene. The resultant reaction mixture is subsequently left to stir at room temperature for 12 hours, then washed successively with 10 ml of 1N hydrochloric acid and 10 ml of saturated sodium hydrogencarbonate solution, and the organic phase is dried over sodium sulfate. After the solvent has been stripped off, the crude product is purified by preparative HPLC, giving 0.31 g (46.4%) of N-[4-(3-oxomorpholin-4-yl)phenyl]-(2R,4R)-1-[2-(4-chlorophenyl)acetyl]-4-hydroxypyrrolidine-2-carboxamide as a white powder, ESI 458, m.p. 141°.

Source