반응 #71842

반응 방정식

trans-2-(Ethoxycarbonyl)cyclopropanecarboxylic acid

WSC

hydrochloric acid ethyl acetate

tert-Butyl 5-{[(4-chloro-5-ethyl-1H-imidazol-2-yl)carbonyl]amino}-1,3-dihydro-2H-isoindole-2-carboxylate

→

title compound

수율 65.0%

Ethyl trans(±)-2-[(5-{[(4-chloro-5-ethyl-1H-imidazol-2-yl)carbonyl]amino}-1,3-dihydro-2H-isoindol-2-yl)carbonyl]cyclopropanecarboxylate

수율 65.0%

용매

methanol

dichloromethane

반응 조건

후처리

1. 1
   기타The solvent was evaporated under reduced pressure
2. 2
   workup.DISSOLUTIONThe resulting residue was dissolved in dichloromethane (5 mL)
3. 3
   workup.STIRRINGthe mixture was stirred at room temperature for one hour
4. 4
   농축The reaction solution was concentrated
5. 5
   workup.ADDITIONdiluted with ethyl acetate
6. 6
   세척washed with water and brine
7. 7
   건조dried over anhydrous magnesium sulfate
8. 8
   농축concentration under reduced pressure
9. 9
   기타the residue was purified by silica gel column chromatography (elution solvent: chloroform/methanol=95/5, 90/10)

실험 절차

tert-Butyl 5-{[(4-chloro-5-ethyl-1H-imidazol-2-yl)carbonyl]amino}-1,3-dihydro-2H-isoindole-2-carboxylate (described in Example (92a), 0.17 g, 0.42 mmol) was dissolved in dichloromethane (3 mL) and methanol (1 mL). A 4 N hydrochloric acid/ethyl acetate solution (15 ml, 60 mmol) was added, followed by stirring for 20 minutes. The solvent was evaporated under reduced pressure. The resulting residue was dissolved in dichloromethane (5 mL) and DMA (5 mL). trans-2-(Ethoxycarbonyl)cyclopropanecarboxylic acid (described in Wessjohann, Ludger A.; Fulhorst, Michael; Zakharova, Svetlana, Pol. J. Chem., 80, 4, 2006, 673-678, 87 mg, 0.55 mmol), WSC (191 mg, 1 mmol) and DMAP (10 mg) were added, and the mixture was stirred at room temperature for one hour. The reaction solution was concentrated, diluted with ethyl acetate, washed with water and brine, and dried over anhydrous magnesium sulfate. Following concentration under reduced pressure, the residue was purified by silica gel column chromatography (elution solvent: chloroform/methanol=95/5, 90/10) to obtain 117 mg of the title compound as a light brown solid (65%).

출처