Sodium Carbonate → methyl 3-cyclohexyl-1-(1,3-dioxolan-2-ylmethyl)-2-(2-formyl-4-methoxyphenyl)-1H-indole-6-carboxylate

HRID 1713997Notes

Reaction equation

HRID 1713997 reaction equation
Br[C:2]1[N:3]([CH2:21][CH:22]2[O:26][CH2:25][CH2:24][O:23]2)[C:4]2[C:9]([C:10]=1[CH:11]1[CH2:16][CH2:15][CH2:14][CH2:13][CH2:12]1)=[CH:8][CH:7]=[C:6]([C:17]([O:19][CH3:20])=[O:18])[CH:5]=2.C([O-])([O-])=O.[Na+].[Na+].[CH3:33][O:34][C:35]1[CH:40]=[CH:39][C:38](B(O)O)=[C:37]([CH:44]=[O:45])[CH:36]=1>O1CCOCC1.[Pd](Cl)Cl.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[CH:11]1([C:10]2[C:9]3[C:4](=[CH:5][C:6]([C:17]([O:19][CH3:20])=[O:18])=[CH:7][CH:8]=3)[N:3]([CH2:21][CH:22]3[O:23][CH2:24][CH2:25][O:26]3)[C:2]=2[C:38]2[CH:39]=[CH:40][C:35]([O:34][CH3:33])=[CH:36][C:37]=2[CH:44]=[O:45])[CH2:16][CH2:15][CH2:14][CH2:13][CH2:12]1

Participants

7

Reactant 3

HCID 10340Sodium CarbonateHCID 27343652-Formyl-4-methoxybenzeneboronic acid2×HCID 68504024HCID 68504024, compound

Product 1

HCID 86604962methyl 3-cyclohexyl-1-(1,3-dioxolan-2-ylmethyl)-2-(2-formyl-4-methoxyphenyl)-1H-indole-6-carboxylateYield 72%

Reagents, catalysts & solvents 3

HCID 6102075Dichlorobis(triphenylphosphine)palladiumCatalystHCID 178418476HCID 178418476, compoundCatalystHCID 312751,4-DioxaneSolvent

Procedure

To a solution of methyl 2-bromo-3-cyclohexyl-1-(1,3-dioxolan-2-ylmethyl)-1H-indole-6-carboxylate in dioxane (0.1 M) was added Na2CO3 (6 eq, 2 M aqueous solution), 4-methoxy-2-formylphenylboronic acid (2 eq) and bis(triphenylphosphine) palladium(II) dichloride (0.2 eq). The mixture was degassed before being heated at reflux for 30 min. RP-HPLC analysis of the reaction mixture showed starting material persisted. The reaction mixture was allowed to cool and an additional 1 eq of 4-methoxy-2-formylphenylboronic acid and 0.1 eq of bis(triphenylphosphine)palladium(II) dichloride introduced. Heating at reflux was then resumed for a further 30 min. The reaction was allowed to cool to RT and partitioned between water and EtOAc. The aqueous fraction was extracted with EtOAc and the combined organics washed with aqueous HCl (1N), water and brine before being dried over Na2SO4, filtered and concentrated in vacuo. The crude material was purified by flash chromatography (10-20% gradient EtOAc/PE) to afford the title compound as a yellow foam (72%); MS (ES+) m/z 478 (M+H)+

Workup

  1. customThe mixture was degassed
  2. temperaturebefore being heated
  3. temperatureat reflux for 30 min
  4. temperatureto cool
  5. temperatureHeating
  6. temperatureat reflux
  7. custompartitioned between water and EtOAc
  8. extractionThe aqueous fraction was extracted with EtOAc
  9. washthe combined organics washed with aqueous HCl (1N), water and brine
  10. dry with materialbefore being dried over Na2SO4
  11. filtrationfiltered
  12. concentrationconcentrated in vacuo
  13. customThe crude material was purified by flash chromatography (10-20% gradient EtOAc/PE)

Sources & evidence

ORD record
ord-301c64ac647e498384b38593d43a4a07
Source dataset
uspto-grants-2010_09
Patent number
US07795247B2

Reaction notes

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