Sodium Carbonate → methyl 3-cyclohexyl-2-(4-fluoro-2-hydroxyphenyl)-1H-indole-6-carboxylate

HRID 1714033Notes

Reaction equation

HRID 1714033 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.N1C2C(=CC=C(C(OC)=O)C=2)C=C1.C([O-])([O-])=O.[Na+].[Na+].[F:40][C:41]1[CH:46]=[CH:45][C:44](B(O)O)=[C:43]([OH:50])[CH:42]=1>COCCOC.CCO.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)[NH:3][C:2]=2[C:44]2[CH:45]=[CH:46][C:41]([F:40])=[CH:42][C:43]=2[OH:50])[CH2:16][CH2:15][CH2:14][CH2:13][CH2:12]1

Participants

8

Reactant 4

HCID 10340Sodium CarbonateHCID 639844Methyl indole-6-carboxylateHCID 3865312(4-Fluoro-2-hydroxy)phenylboronic acidHCID 11175076Methyl 2-bromo-3-cyclohexyl-1H-indole-6-carboxylate

Product 1

HCID 67343580methyl 3-cyclohexyl-2-(4-fluoro-2-hydroxyphenyl)-1H-indole-6-carboxylateYield 61%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 702EthanolSolventHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
100 °C

Procedure

To a solution of methyl 2-bromo-3-cyclohexyl-1H-indole-6-carboxylate (prepared as described in WO2004087714 from commercially available methyl indole-6-carboxylate) in a mixture of DME and EtOH (5:2, v/v, 0.2 M) were added 2.6 eq. of Na2CO3 (2 M aqueous solution), 1.3 eq. of 4-fluoro-2-hydroxy-phenylboronic acid and 0.1 eq. of tetrakis(triphenylphosphine)palladium(0). The mixture was degassed thoroughly with a stream of argon and then heated to 100° C. overnight. The reaction mixture was allowed to cool to RT, diluted with EtOAc and washed with 1N hydrochloric acid and with brine, dried over Na2SO4 and concentrated in vacuo. The crude material was purified by flash chromatography (1:5 EtOAc/PE) to afford the title compound as a beige solid (61%); MS (ES+) m/z 368 (M+H)+.

Workup

  1. customThe mixture was degassed thoroughly with a stream of argon
  2. temperatureto cool to RT
  3. additiondiluted with EtOAc
  4. washwashed with 1N hydrochloric acid and with brine
  5. dry with materialdried over Na2SO4
  6. concentrationconcentrated in vacuo
  7. customThe crude material was purified by flash chromatography (1:5 EtOAc/PE)

Sources & evidence

ORD record
ord-74f0f1b2c67240bf92e2d6cb8c77c717
Source dataset
uspto-grants-2010_09
Patent number
US07795247B2

Reaction notes

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