Sodium Carbonate → methyl 11-cyclohexyl-6-hydroxy-8-methoxy-6H-isoindolo[2,1-a]indole-3-carboxylate

HRID 1453364Notes

Reaction equation

HRID 1453364 reaction equation
Br[C:2]1[NH:3][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.[CH3:21][O:22][C:23]1[CH:28]=[CH:27][C:26](B(O)O)=[C:25]([CH:32]=[O:33])[CH:24]=1.[Li+].[Cl-].C([O-])([O-])=O.[Na+].[Na+]>CCO.C1(C)C=CC=CC=1.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=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]3[CH:32]([OH:33])[C:25]4[C:26]([C:2]=23)=[CH:27][CH:28]=[C:23]([O:22][CH3:21])[CH:24]=4)[CH2:16][CH2:15][CH2:14][CH2:13][CH2:12]1

Participants

7

Reactant 4

HCID 10340Sodium CarbonateHCID 433294Lithium ChlorideHCID 27343652-Formyl-4-methoxybenzeneboronic acidHCID 11175076Methyl 2-bromo-3-cyclohexyl-1H-indole-6-carboxylate

Product 1

HCID 59682118methyl 11-cyclohexyl-6-hydroxy-8-methoxy-6H-isoindolo[2,1-a]indole-3-carboxylateYield 63%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 21863594Toluene ethanolSolvent

Conditions

Temperature
100 °C

Procedure

To a slurried solution of methyl 2-bromo-3-cyclohexyl-1H-indole-6-carboxylate (4.3 g, 13 mmol), 4-methoxy-2-formylphenylboronic acid (3.0 g, 17 mmol) and LiCl (2.2 g, 51 mmol) in EtOH/toluene (1:1, 100 mL) was added Pd(PPh3)4 (1.4 g, 1.3 mmol) and then 1M Na2CO3 (aq.) (32 mL, 32 mmol). The reaction solution was flushed with nitrogen and heated at 100° C. for 3 h and cooled to rt. The reaction was concentrated to remove EtOH, diluted with H2O (200 mL) and extracted with EtOAc (2×150 mL). The combined organics were washed with brine (100 mL), dried (MgSO4), filtered and concentrated to dryness. The residue was triturated with CH2Cl2 and the solids were collected by filtrated and washed with Et2O and CH2Cl2 to yield methyl 11-cyclohexyl-6-hydroxy-8-methoxy-6H-isoindolo[2,1-a]indole-3-carboxylate (3.0 g, 8.0 mmol, 63%) as a yellow solid which was used without further purification. LCMS: m/e 374 (M+H)+, ret time 3.09 min, column B, 3 minute gradient.

Workup

  1. customThe reaction solution was flushed with nitrogen
  2. temperaturecooled to rt
  3. concentrationThe reaction was concentrated
  4. customto remove EtOH
  5. additiondiluted with H2O (200 mL)
  6. extractionextracted with EtOAc (2×150 mL)
  7. washThe combined organics were washed with brine (100 mL)
  8. dry with materialdried (MgSO4)
  9. filtrationfiltered
  10. concentrationconcentrated to dryness
  11. customThe residue was triturated with CH2Cl2
  12. customthe solids were collected
  13. filtrationby filtrated
  14. washwashed with Et2O and CH2Cl2

Sources & evidence

ORD record
ord-0b6c6bea8b1d467b8740cd99776c64c5
Source dataset
uspto-grants-2009_01
Patent number
US07473688B2

Reaction notes

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