Reaction #85599

Reaction equation

2,2,6,6-Tetramethylpiperidine

N,N′,N″,N″-pentamethyldiethylene triamine

compound 1

4-methylcatechol

n-BuLi

THF

1,1,2-trichloro-1,2,2-trifluoroethane

→

title compound

Yield 73.8%

4-chloro-5-fluoro-1H-indole-3-carboxylic acid

Yield 73.8%

Solvents

Water

—

hexanes

Conditions

Workup

1. 1
   Temperaturewas warmed to 25° C
2. 2
   WashThe organic phase was washed with brine
3. 3
   Dryingdried with sodium sulfate
4. 4
   Filtrationfiltered
5. 5
   Concentrationconcentrated in vacuo
6. 6
   OtherThe residue was purified by SiO2 column chromatography (PE)

Procedure

2,2,6,6-Tetramethylpiperidine (1.06 g, 7.5 mmol), N,N′,N″,N″-pentamethyldiethylene triamine (3.46 g, 20 mmol) and compound 1 (1.45 g, 5.0 mmol) were added consecutively to a solution of n-BuLi (2.5 M in hexanes, 8 mL, 20 mmol) in THF (20 mL) and hexanes (6 mL) at −78° C. After stirring for 4 h at −78° C., the mixture was treated with 1,1,2-trichloro-1,2,2-trifluoroethane (1.18 g, 6.0 mmol) before it was warmed to 25° C. Water was added to the mixture. The organic phase was washed with brine, dried with sodium sulfate, filtered, and concentrated in vacuo. The residue was purified by SiO2 column chromatography (PE) to provide title compound (1.2 g, 73.8%) as a colorless liquid.

Source