Hexane → 5-Chloro-3-[4-(5,5-dimethyl[1,3]dioxan-2-yl)-2-methoxyphenyl]-3-hydroxy-1,3-dihydro-indol-2-one

HRID 2361839Notes

Reaction equation

HRID 2361839 reaction equation
C([Li])CCC.CCCCCC.I[C:13]1[CH:18]=[CH:17][C:16]([CH:19]2[O:24][CH2:23][C:22]([CH3:26])([CH3:25])[CH2:21][O:20]2)=[CH:15][C:14]=1[O:27][CH3:28].[Na].[Cl:30][C:31]1[CH:32]=[C:33]2[C:37](=[CH:38][CH:39]=1)[NH:36][C:35](=[O:40])[C:34]2=[O:41].ClC1C=C2C(=CC=1)NC(=O)C2=O.[H-].[Na+].[Cl-].[NH4+]>C1COCC1>[Cl:30][C:31]1[CH:32]=[C:33]2[C:37](=[CH:38][CH:39]=1)[NH:36][C:35](=[O:40])[C:34]2([C:13]1[CH:18]=[CH:17][C:16]([CH:19]2[O:24][CH2:23][C:22]([CH3:26])([CH3:25])[CH2:21][O:20]2)=[CH:15][C:14]=1[O:27][CH3:28])[OH:41]

Participants

9

Reactant 7

HCID 8058HexaneHCID 24758Sodium hydrideHCID 25517Ammonium ChlorideHCID 872035-chloro-1H-indole-2,3-dioneHCID 594689832-(4-Iodo-3-methoxyphenyl)-5,5-dimethyl[1,3]dioxaneHCID 670430655-Chlorisatin sodium saltHCID 178418339Butyllithium

Product 1

HCID 670433285-Chloro-3-[4-(5,5-dimethyl[1,3]dioxan-2-yl)-2-methoxyphenyl]-3-hydroxy-1,3-dihydro-indol-2-one

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

A solution of n-butyllithium in hexane (1.6 m, 5.52 ml, 8.83 mmol) was slowly added dropwise to a solution of 2-(4-iodo-3-methoxyphenyl)-5,5-dimethyl[1,3]dioxane (3.00 g, 8.62 mmol) in THF (100 ml) at −78° C. After 15 min, a solution of 5-chloroisatin sodium salt [prepared by treating a solution of 5-chloroisatin (1.21 g, 6.64 mmol) in THF with one equivalent of sodium hydride at 0° C. for one h] was added dropwise to the solution of the organolithium species. The reaction mixture is allowed to warm to room temperature and then stirred for one further hour. Aqueous ammonium chloride solution was added to the reaction solution with stirring, and the mixture was extracted with ethyl acetate. The combined organic phase was washed with water and saturated sodium chloride solution, dried over magnesium sulfate and concentrated under reduced pressure. The desired product crystallizes on standing in the cold. Yield: 1.42 g (53%) of a white solid. MS (API-ES, pos) m/z=404 [M+H]+

Workup

  1. stirringwith stirring
  2. extractionthe mixture was extracted with ethyl acetate
  3. washThe combined organic phase was washed with water and saturated sodium chloride solution
  4. dry with materialdried over magnesium sulfate
  5. concentrationconcentrated under reduced pressure
  6. customThe desired product crystallizes

Sources & evidence

ORD record
ord-6c0099d1028947a68dd7676117be1eaf
Source dataset
uspto-grants-2014_04
Patent number
US08691815B2

Reaction notes

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