Sodium Carbonate → methyl 1-{2-[bis(tert-butoxycarbonyl)amino]-3-methoxy-3-oxopropyl}-3-cyclohexyl-2-(2-formylphenyl)-1H-indole-6-carboxylate

HRID 1518224Notes

Reaction equation

HRID 1518224 reaction equation
[C:1]([O:5][C:6]([N:8]([C:35]([O:37][C:38]([CH3:41])([CH3:40])[CH3:39])=[O:36])[CH:9]([C:31]([O:33][CH3:34])=[O:32])[CH2:10][N:11]1[C:19]2[C:14](=[CH:15][CH:16]=[C:17]([C:20]([O:22][CH3:23])=[O:21])[CH:18]=2)[C:13]([CH:24]2[CH2:29][CH2:28][CH2:27][CH2:26][CH2:25]2)=[C:12]1Br)=[O:7])([CH3:4])([CH3:3])[CH3:2].C([O-])([O-])=O.[Na+].[Na+].[CH:48]([C:50]1[CH:55]=[CH:54][CH:53]=[CH:52][C:51]=1B(O)O)=[O:49]>O1CCOCC1.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[C:1]([O:5][C:6]([N:8]([C:35]([O:37][C:38]([CH3:41])([CH3:40])[CH3:39])=[O:36])[CH:9]([C:31]([O:33][CH3:34])=[O:32])[CH2:10][N:11]1[C:19]2[C:14](=[CH:15][CH:16]=[C:17]([C:20]([O:22][CH3:23])=[O:21])[CH:18]=2)[C:13]([CH:24]2[CH2:29][CH2:28][CH2:27][CH2:26][CH2:25]2)=[C:12]1[C:51]1[CH:52]=[CH:53][CH:54]=[CH:55][C:50]=1[CH:48]=[O:49])=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 2921892-Formylphenylboronic acidHCID 68699898methyl 1-{2-[bis(tert-butoxycarbonyl)amino]-3-methoxy-3-oxopropyl}-2-bromo-3-cyclohexyl-1H-indole-6-carboxylate

Product 1

HCID 86637854methyl 1-{2-[bis(tert-butoxycarbonyl)amino]-3-methoxy-3-oxopropyl}-3-cyclohexyl-2-(2-formylphenyl)-1H-indole-6-carboxylateYield 65%

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalystHCID 312751,4-DioxaneSolvent

Procedure

To a solution of methyl 1-{2-[bis(tert-butoxycarbonyl)amino]-3-methoxy-3-oxopropyl}-2-bromo-3-cyclohexyl-1H-indole-6-carboxylate in dioxane (0.15 M) were added 6 eq of Na2CO3 (2 M aqueous solution), 1.5 eq (2-formylphenyl)boronic acid and 0.2 eq of bis(triphenylphosphine)palladium(II) dichloride. The mixture was heated at reflux for 1.5 h. The reaction mixture was filtered and then the filtrate was diluted with EtOAc. The organic phase was washed with H2O, brine and dried over Na2SO4 before being filtered and concentrated in vacuo. The crude was purified by flash chromatography (Biotage cartridge, 1.0:9.0 EtOAc/PE) to afford the title compound (65%). MS (ES+) m/z 663 (M+H)+.

Workup

  1. temperatureThe mixture was heated
  2. temperatureat reflux for 1.5 h
  3. filtrationThe reaction mixture was filtered
  4. additionthe filtrate was diluted with EtOAc
  5. washThe organic phase was washed with H2O, brine
  6. dry with materialdried over Na2SO4
  7. filtrationbefore being filtered
  8. concentrationconcentrated in vacuo
  9. customThe crude was purified by flash chromatography (Biotage cartridge, 1.0:9.0 EtOAc/PE)

Sources & evidence

ORD record
ord-523d33ae50b2474c8db494e429c9c06b
Source dataset
uspto-grants-2012_07
Patent number
US08232390B2

Reaction notes

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