Reaction #47525

Reaction equation

(E)-3-(2-benzyloxy-phenoxy)-4-bromo-but-2-enoic acid ethyl ester

(S)-2-amino-3-cyclohexyl-propionic acid methyl ester

N,N-diisopropylethylamine

→

(S)-2-[4-(2-benzyloxy-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-3-cyclohexyl-propionic acid methyl ester

Yield 16.0%

Solvents

N,N-dimethylformamide

Conditions

Workup

1. 1
   Temperaturethe reaction mixture was heated at 110° C.-120° C. for 16 h
2. 2
   Extractionthe resulting mixture was extracted with ethyl acetate
3. 3
   WashThe combined organic layers were washed with a saturated aqueous sodium chloride solution
4. 4
   Dryingdried over sodium sulfate
5. 5
   Concentrationconcentrated in vacuo
6. 6
   OtherPurification by flash column chromatography (silica gel (100-200 mesh))

Procedure

To a stirred solution of (S)-2-amino-3-cyclohexyl-propionic acid methyl ester (1.05 g, 0.006 mol) in N,N-dimethylformamide (8 mL) was added N,N-diisopropylethylamine (3.30 g, 0.026 mol) slowly at room temperature, under nitrogen. The resulting mixture was stirred for 5 min and then treated with (E)-3-(2-benzyloxy-phenoxy)-4-bromo-but-2-enoic acid ethyl ester (2.00 g, 0.005 mol) and the reaction mixture was heated at 110° C.-120° C. for 16 h. After this time, ice water was added and the resulting mixture was extracted with ethyl acetate. The combined organic layers were washed with a saturated aqueous sodium chloride solution, dried over sodium sulfate and concentrated in vacuo. Purification by flash column chromatography (silica gel (100-200 mesh)) afforded (S)-2-[4-(2-benzyloxy-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-3-cyclohexyl-propionic acid methyl ester (360 mg, 14%) as a yellow oil.

Source