Diethyl Ether → 2-[5-Chloro-3-(2-methoxyphenyl)-6-methyl-2-oxo-2,3-dihydro-1h-indol-3-yl]acetic acid

HRID 1243319Notes

Reaction equation

HRID 1243319 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9](=[O:11])[O-])=[CH:4][C:3]=1[CH3:12].C([Li])(C)(C)C.CO[C:20]1[CH:25]=[CH:24][CH:23]=C[C:21]=1[C:26](=O)[C:27]([O:29]CC)=[O:28].[NH4+].[Cl-].C[CH2:36][O:37][CH2:38][CH3:39]>CCCCC.C1COCC1>[Cl:1][C:2]1[CH:7]=[C:6]2[C:5](=[CH:4][C:3]=1[CH3:12])[NH:8][C:9](=[O:11])[C:21]2([CH2:26][C:27]([OH:29])=[O:28])[C:20]1[CH:25]=[CH:24][CH:23]=[CH:39][C:38]=1[O:37][CH3:36]

Participants

8

Reactant 5

HCID 3283Diethyl EtherHCID 25517Ammonium ChlorideHCID 15579652Ethyl 2-methoxybenzoylformateHCID 219254184-Chloro-3-methylphenylcarbamateHCID 178418306HCID 178418306, compound

Product 1

HCID 219254152-[5-Chloro-3-(2-methoxyphenyl)-6-methyl-2-oxo-2,3-dihydro-1h-indol-3-yl]acetic acid

Reagents, catalysts & solvents 2

HCID 8003PentaneSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-70 °C

Procedure

4-chloro-3-methylphenylcarbamate in 45 ml of ether is cooled to −70° C., under an argon atmosphere, 30 ml of 1.5M solution of tert-butyllithium in pentane are added dropwise, the mixture is stirred for 1 hour while allowing the temperature to rise to −10° C., and is stirred 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, the mixture is stirred for 1 hour and allowed to warm to −30° C., and is then stirred overnight while allowing the temperature to return 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 filtered off by suction. 2.6 g of the expected product are obtained, m.p.=254–256° C.

Workup

  1. customto rise to −10° C.
  2. stirringis stirred for 1 hour 45 minutes at −10° C
  3. stirringthe mixture is stirred for 1 hour
  4. temperatureto warm to −30° C.
  5. stirringis then stirred overnight
  6. customto return to RT
  7. customthe THF is evaporated off
  8. extractionthe resulting aqueous phase is extracted three times with EtOAc
  9. washthe organic phase is washed with water, with saturated NaCl solution
  10. dry with materialdried over Na2SO4
  11. customthe solvent is partially evaporated off
  12. filtrationthe crystalline product is filtered off by suction

Sources & evidence

ORD record
ord-4a3696a1ab0b440f9ab5df85171e88f9
Source dataset
uspto-grants-2006_10
Patent number
US07119086B2

Reaction notes

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