تفاعل #46444

معادلة التفاعل

NaOMe

2-bromo-4-fluoro-benzaldehyde

methyl azidoacetate

→

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

المردود 68.2%

المذيبات

methanol

MeOH

ظروف التفاعل

المعالجة

1. 1
   أخرىequipped with stirrer
2. 2
   درجة الحرارةbefore warming up to room temperature
3. 3
   workup.STIRRINGAfter stirring another 3 hours
4. 4
   أخرىthe reaction solvent was removed under reduced pressure
5. 5
   workup.ADDITIONThe residue was added to xylene (15 ml)
6. 6
   غسيلthe organic phase was washed with H2O, brine
7. 7
   تجفيفby drying over MgSO4
8. 8
   workup.ADDITIONThe resulting solution was added dropwise to a flask of xylene (30 ml)
9. 9
   درجة الحرارةthe solution was heated
10. 10
    درجة الحرارةat reflux overnight
11. 11
    درجة الحرارةAfter cooling to room temperature
12. 12
    غسيلthe reaction mixture was washed with H2O, and xylene
13. 13
    أخرىwas removed under reduced pressure

الإجراء التجريبي

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)−.

المصدر