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

HRID 2712

Reaction equation

HRID 2712 reaction equation
[O:1]=[C:2]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[C:4](=[O:11])[N:3]1[CH:12]([CH2:16][C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=1[CH:23]=[CH2:24])[C:13]([OH:15])=[O:14].N1C=CC=CC=1.[CH3:31][Si:32]([CH3:37])([CH3:36])[CH2:33][CH2:34]O.Cl.CN(C)CCCN=C=NCC>O1CCCC1.C(OCC)(=O)C>[O:1]=[C:2]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[C:4](=[O:11])[N:3]1[CH:12]([CH2:16][C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=1[CH:23]=[CH2:24])[C:13]([O:15][CH2:34][CH2:33][Si:32]([CH3:37])([CH3:36])[CH3:31])=[O:14]

Participants

7

Reactant 4

HCID 1049PyridineHCID 180132-(Trimethylsilyl)ethanolHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 186125162-(1,3-Dioxo-1,3-dihydro-isoindol-2-yl)-3-(2-vinyl-phenyl)-propionic acid

Product 1

HCID 541575632-(1,3-Dioxo-1,3-dihydro-isoindol-2-yl)-3-(2-vinyl-phenyl)-propionic acid, 2-trimethylsilanyl-ethyl esterYield 81%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

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%).

Workup

  1. temperaturecool in an ice bath
  2. stirringStir for 22 hours at 5° C.
  3. waitat room temperature for 1.5 hours
  4. additionadd 0.6 times all reagents
  5. stirringstir at room temperature overnight
  6. washwash with 5% sulfuric acid (40 mL) and saturated sodium hydrogen carbonate (40 mL)
  7. extractionBack extract with methylene chloride (100 mL)
  8. washwash with brine (30 mL)
  9. dry with materialdry (Na2SO4)
  10. customEvaporate the solvent in vacuo
  11. custompurify by silica gel chromatography (2:1 hexane/ethyl acetate)

Sources & evidence

ORD record
ord-f82b850c17b44c82bd3c88a18c85d0b3
Source dataset
uspto-grants-1998_03
Patent number
US05731306

Linked notes

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