반응 #46444

반응 방정식

NaOMe

2-bromo-4-fluoro-benzaldehyde

methyl azidoacetate

→

4-bromo-6-fluoro-1H-indole-2-carboxylic acid methyl ester

수율 68.2%

용매

methanol

MeOH

반응 조건

후처리

1. 1
   기타equipped with stirrer
2. 2
   온도before warming up to room temperature
3. 3
   workup.STIRRINGAfter stirring another 3 hours
4. 4
   기타the reaction solvent was removed under reduced pressure
5. 5
   workup.ADDITIONThe residue was added to xylene (15 ml)
6. 6
   세척the organic phase was washed with H2O, brine
7. 7
   건조by drying over MgSO4
8. 8
   workup.ADDITIONThe resulting solution was added dropwise to a flask of xylene (30 ml)
9. 9
   온도the solution was heated
10. 10
    온도at reflux overnight
11. 11
    온도After cooling to room temperature
12. 12
    세척the reaction mixture was washed with H2O, and xylene
13. 13
    기타was removed under reduced pressure

실험 절차

Dry methanol (5 ml) and NaOMe (0.9 ml, 3.93 mmol, 25% wt in MeOH) were added to a three-neck flask equipped with stirrer, low-temperature thermometer, and nitrogen line. The resulting solution was cooled in a dry ice/CH3CN bath to −40° C. A solution of 2-bromo-4-fluoro-benzaldehyde (195 mg, 0.96 mmol) and methyl azidoacetate (450 mg, 3.9 mmol) in dry MeOH (5 ml) was added dropwise. The mixture was allowed to stir at −40° C. for 30 minutes before warming up to room temperature. After stirring another 3 hours, the reaction solvent was removed under reduced pressure. The residue was added to xylene (15 ml), and the organic phase was washed with H2O, brine, followed by drying over MgSO4. The resulting solution was added dropwise to a flask of xylene (30 ml) and the solution was heated at reflux overnight. After cooling to room temperature, the reaction mixture was washed with H2O, and xylene was removed under reduced pressure to give 4-bromo-6-fluoro-1H-indole-2-carboxylic acid methyl ester as a white solid (178 mg, 68%). MS: 272.1 (M−H)−.

출처