Reaction #59633

Reaction equation

compound

Ethyl 2-(2-methoxyphenyl)-2-oxoacetate

tert-butyllithium

tert-butyl 4-chloro-3-methylphenylcarbamate

NH4Cl

→

expected product

3,5-Dichloro-3-(2-methoxyphenyl)-6-methyl-1,3-dihydro-2H-indol-2-one

Solvents

THF

pentane

ether

Conditions

Workup

1. 1
   workup.WAITthe mixture is left
2. 2
   Otherto rise to −10° C.
3. 3
   workup.WAITis left
4. 4
   workup.STIRRINGstirring for 1 hour 45 minutes at −10° C
5. 5
   workup.WAITthe mixture is left
6. 6
   workup.STIRRINGstirring for 1 hour
7. 7
   Otherto rise to −30° C.
8. 8
   workup.STIRRINGis then stirred overnight
9. 9
   Otherto rise to RT
10. 10
    Otherthe THF is evaporated off
11. 11
    Extractionthe resulting aqueous phase is extracted three times with EtOAc
12. 12
    Washthe organic phase is washed with water, with saturated NaCl solution
13. 13
    Dryingdried over Na2SO4
14. 14
    Otherthe solvent is partially evaporated off
15. 15
    Filtrationthe crystalline product is spin-filtered off

Procedure

A solution of 5 g of tert-butyl 4-chloro-3-methylphenylcarbamate in 45 ml of ether is cooled to −70° C. under an argon atmosphere, 30 ml of a 1.5M solution of tert-butyllithium in pentane are added dropwise, the mixture is left stirring for 1 hour while allowing the temperature to rise to −10° C., and is left stirring for 1 hour 45 minutes at −10° C. The reaction mixture is cooled to −70° C., a solution of 5 g of the compound obtained in step A in 25 ml of THF is added dropwise and the mixture is left stirring for 1 hour while allowing the temperature to rise to −30° C., and is then stirred overnight while allowing the temperature to rise to RT. Saturated NH4Cl solution is added to the reaction mixture, the THF is evaporated off, the resulting aqueous phase is extracted three times with EtOAc, the organic phase is washed with water, with saturated NaCl solution and dried over Na2SO4, the solvent is partially evaporated off and the crystalline product is spin-filtered off. 2.6 g of the expected product are obtained; m.p.=254-256° C.

Source