Sodium Carbonate → methyl 3-cyclohexyl-2-(4-methoxy-2-{[(triisopropylsilyl)oxy]methyl}phenyl)-1H-indole-6-carboxylate

HRID 1669430Notes

Reaction equation

HRID 1669430 reaction equation
[CH3:1][O:2][C:3]([C:5]1[CH:13]=[C:12]2[C:8]([C:9]([CH:15]3[CH2:20][CH2:19][CH2:18][CH2:17][CH2:16]3)=[C:10](Br)[NH:11]2)=[CH:7][CH:6]=1)=[O:4].N1C2C(=CC=C(C(OC)=O)C=2)C=C1.[CH3:34][O:35][C:36]1[CH:41]=[CH:40][C:39](B(O)O)=[C:38]([CH2:45][O:46][Si:47]([CH:54]([CH3:56])[CH3:55])([CH:51]([CH3:53])[CH3:52])[CH:48]([CH3:50])[CH3:49])[CH:37]=1.C([O-])([O-])=O.[Na+].[Na+]>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>[CH:15]1([C:9]2[C:8]3[C:12](=[CH:13][C:5]([C:3]([O:2][CH3:1])=[O:4])=[CH:6][CH:7]=3)[NH:11][C:10]=2[C:39]2[CH:40]=[CH:41][C:36]([O:35][CH3:34])=[CH:37][C:38]=2[CH2:45][O:46][Si:47]([CH:48]([CH3:50])[CH3:49])([CH:54]([CH3:56])[CH3:55])[CH:51]([CH3:53])[CH3:52])[CH2:20][CH2:19][CH2:18][CH2:17][CH2:16]1

Participants

7

Reactant 4

HCID 10340Sodium CarbonateHCID 639844Methyl indole-6-carboxylateHCID 11175076Methyl 2-bromo-3-cyclohexyl-1H-indole-6-carboxylateHCID 67345879(4-Methoxy-2-{[(triisopropylsilyl)oxy]methyl}phenyl)boronic acid

Product 1

HCID 67345419methyl 3-cyclohexyl-2-(4-methoxy-2-{[(triisopropylsilyl)oxy]methyl}phenyl)-1H-indole-6-carboxylateYield 81%

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
110 °C

Procedure

Methyl-2-bromo-3-cyclohexyl-1H-indole-6-carboxylate (prepared as described in International patent application WO2004/087714 from commercially available methyl indole-6-carboxylate) and (4-methoxy-2-{[(triisopropylsilyl)oxy]methyl}phenyl)boronic acid (1.1 eq) were dissolved in dioxane (0.125M solution) and 2M aq. Na2CO3 solution (3.3 eq) was added. The mixture was degassed and flushed with argon. Then Pd(PPh3)2Cl2 (0.1 eq) was added and the mixture was heated under argon atmosphere to 110° C. After 5 h at this temperature all volatiles were evaporated in vacuo and the residual material was dissolved in EtOAc. The solution was extracted with water and with brine, then dried over Na2SO4 and evaporated in vacuo. The residual material was purified by FC (PE:EtOAc, 9:1). After evaporation of the solvents the product was obtained as an off-white foam (81%). The material was used without further characterization in the next reaction.

Workup

  1. customThe mixture was degassed
  2. customflushed with argon
  3. customAfter 5 h at this temperature all volatiles were evaporated in vacuo
  4. dissolutionthe residual material was dissolved in EtOAc
  5. extractionThe solution was extracted with water and with brine
  6. dry with materialdried over Na2SO4
  7. customevaporated in vacuo
  8. customThe residual material was purified by FC (PE:EtOAc, 9:1)
  9. customAfter evaporation of the solvents the product

Sources & evidence

ORD record
ord-b0cc095db4904551b00e1131354d055c
Source dataset
uspto-grants-2011_08
Patent number
US07989438B2

Reaction notes

Loading…