Toluene → HCID 135985223, compound

HRID 1394859Notes

Reaction equation

HRID 1394859 reaction equation
[NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[C:7]([C:10]([OH:12])=[O:11])[CH:8]=2)[CH:3]=[CH:2]1.Br[C:14]1[N:15]([CH2:21][O:22][CH2:23][CH2:24][Si:25]([CH3:28])([CH3:27])[CH3:26])[C:16]([Br:20])=[C:17]([Br:19])[N:18]=1.[Li+].[Cl-].[C:31]([O-])([O-])=O.[Na+].[Na+].[C:37]1(C)[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=1>C(O)C.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.CCOC(C)=O.CCCCCC.O.CCOC(C)=O>[CH:37]1([C:3]2[C:4]3[C:9](=[CH:8][C:7]([C:10]([O:12][CH3:31])=[O:11])=[CH:6][CH:5]=3)[NH:1][C:2]=2[C:14]2[N:15]([CH2:21][O:22][CH2:23][CH2:24][Si:25]([CH3:28])([CH3:27])[CH3:26])[C:16]([Br:20])=[C:17]([Br:19])[N:18]=2)[CH2:42][CH2:41][CH2:40][CH2:39][CH2:38]1

Participants

11

Reactant 5

HCID 1140TolueneHCID 10340Sodium CarbonateHCID 433294Lithium ChlorideHCID 5952301H-indole-6-carboxylic acidHCID 109062032,4,5-tribromo-1-[[2-(trimethylsilyl)ethoxy]methyl]-1H-Imidazole

Product 1

HCID 135985223HCID 135985223, compound

Reagents, catalysts & solvents 5

HCID 178418397HCID 178418397, compoundCatalystHCID 702EthanolSolventHCID 962WaterSolventHCID 8857Ethyl AcetateSolventHCID 21226206Ethyl acetate hexaneSolvent

Conditions

Temperature
80 °C

Procedure

1H-indole-6-carboxylic acid, 3-cyclohexyl-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-, methyl ester. (383 mg, 1.0 mmol), 2,4,5-tribromo-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazole (435.2 mg, 1.0 mmol) and LiCl (84 mg, 2.0 mmol) were dissolved in a mixture of ethanol (4 mL) and toluene (4 mL). An aqueous Na2CO3 solution (1M, 2.5 mL, 2.5 mmol) was added and the mixture degassed with nitrogen for 20 min. Pd(PPh3)4 (11.5 mg, 0.1 mmol) was then added and the mixture stirred at 80° C. under N2 for 3-4 h. EtOAc (6 mL) was added, followed by 20 mL of water. The organic layer was separated, dried (Na2SO4), filtered and evaporated under reduced pressure to give a residue. This was subjected to flash chromatography on silica gel ((EtOAc-Hexane 1:3) to afford 435 (71%) of the title compound as a foam. 1H NMR (300 MHz, CDCl3) δ 0.04 (s, 9H), 1.02 (t, 2H, J=8.4 Hz), 1.20-2.00 (m, 10H), 3.31 (m, 1H), 3.76 (t, 2H, J=8.4 Hz), 3.91 (s, 3H), 5.36 (s, 2H), 7.73 (dd, 1H, J=1.5, 8.5 Hz), 7.88 (d, 1H, J=8.5 Hz), 8.07 (s, 1H).

Workup

  1. customthe mixture degassed with nitrogen for 20 min
  2. customThe organic layer was separated
  3. dry with materialdried (Na2SO4)
  4. filtrationfiltered
  5. customevaporated under reduced pressure
  6. customto give a residue

Sources & evidence

ORD record
ord-683869ea68854eb18ff34762163cdfac
Source dataset
uspto-grants-2008_03
Patent number
US07348425B2

Reaction notes

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