Ammonium Chloride → 3,5-Dichloro-3-(2,3-dimethoxyphenyl)-1,3-dihydro-2h-indol-2-one

HRID 1581706Notes

Reaction equation

HRID 1581706 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9](=[O:15])OC(C)(C)C)=[CH:4][CH:3]=1.C([Li])(C)(C)C.[CH3:21][O:22][C:23]1[C:28]([O:29][CH3:30])=[CH:27][CH:26]=[CH:25][C:24]=1[C:31](=O)C(OCC)=O.[NH4+].[Cl-:39]>CCOCC.CCCCC.C1COCC1>[Cl:39][C:31]1([C:24]2[CH:25]=[CH:26][CH:27]=[C:28]([O:29][CH3:30])[C:23]=2[O:22][CH3:21])[C:4]2[C:5](=[CH:6][CH:7]=[C:2]([Cl:1])[CH:3]=2)[NH:8][C:9]1=[O:15]

Participants

8

Reactant 4

HCID 25517Ammonium ChlorideHCID 546372tert-butyl N-(4-chlorophenyl)carbamateHCID 21905960Ethyl 2-(2,3-dimethoxyphenyl)-2-oxoacetateHCID 178418306HCID 178418306, compound

Product 1

HCID 219059313,5-Dichloro-3-(2,3-dimethoxyphenyl)-1,3-dihydro-2h-indol-2-one

Reagents, catalysts & solvents 3

HCID 3283Diethyl EtherSolventHCID 8003PentaneSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-40 °C

Procedure

A mixture of 11.4 g of tert-butyl 4-chlorophenylcarbamate in 100 ml of ether is cooled to −40° C., under an atmosphere of dry nitrogen, 80 ml of a 1.5 M solution of tert-butyllithium in pentane are added dropwise and the mixture is stirred at −20° C. for 3 hours. The reaction mixture is cooled to −40° C., a solution of 14 g of the compound obtained in step A in 50 ml of THF is added over one hour and the mixture is stirred for 4 days at RT. The reaction mixture is poured into saturated NH4Cl solution and the precipitate formed is spin-filtered off and dried. 10.2 g of the expected product are obtained and are used in the next step without further purification.

Workup

  1. temperatureThe reaction mixture is cooled to −40° C.
  2. stirringthe mixture is stirred for 4 days at RT
  3. customthe precipitate formed
  4. filtrationis spin-filtered off
  5. customdried

Sources & evidence

ORD record
ord-65df106d5dfc423cb5c5fa402d48ff1e
Source dataset
uspto-grants-2004_05
Patent number
US06730695B2

Reaction notes

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