Reaction #2808

Reaction equation

1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride

pyridine

2-(trimethylsilyl)ethanol

2-(1,3-dioxo-1,3-dihydro-isoindol-2-yl)-3-(2-vinyl-phenyl)-propionic acid

→

title compound

Yield 81.0%

2-(1,3-Dioxo-1,3-dihydro-isoindol-2-yl)-3-(2-vinyl-phenyl)-propionic acid, 2-trimethylsilanyl-ethyl ester

Yield 81.0%

Solvents

ethyl acetate

tetrahydrofuran

Conditions

Workup

1. 1
   Temperaturecool in an ice bath
2. 2
   workup.STIRRINGStir for 22 hours at 5° C.
3. 3
   workup.WAITat room temperature for 1.5 hours
4. 4
   workup.ADDITIONadd 0.6 times all reagents
5. 5
   workup.STIRRINGstir at room temperature overnight
6. 6
   Washwash with 5% sulfuric acid (40 mL) and saturated sodium hydrogen carbonate (40 mL)
7. 7
   ExtractionBack extract with methylene chloride (100 mL)
8. 8
   Washwash with brine (30 mL)
9. 9
   Dryingdry (Na2SO4)
10. 10
    OtherEvaporate the solvent in vacuo
11. 11
    Otherpurify by silica gel chromatography (2:1 hexane/ethyl acetate)

Procedure

Dissolve 2-(1,3-dioxo-1,3-dihydro-isoindol-2-yl)-3-(2-vinyl-phenyl)-propionic acid (2.47 g, 7.69 mmol) in tetrahydrofuran (35 mL) and cool in an ice bath. Treat with pyridine (1.6 mL, 20 mmol) and 2-(trimethylsilyl)ethanol (2.3 mL, 16 mmol). Stir for 30 minutes and add 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDC) (2.21 g, 11.5 mmol). Stir for 22 hours at 5° C., then at room temperature for 1.5 hours. Cool to 0° C., add 0.6 times all reagents and stir at room temperature overnight. Dilute with ethyl acetate (150 mL), wash with 5% sulfuric acid (40 mL) and saturated sodium hydrogen carbonate (40 mL). Back extract with methylene chloride (100 mL), wash with brine (30 mL) and dry (Na2SO4). Evaporate the solvent in vacuo and purify by silica gel chromatography (2:1 hexane/ethyl acetate) to give the title compound (2.61 g, 81%).

Source