Potassium Carbonate → methyl 6-chloro-5-(2'-hydroxybiphenyl-4-yl)-1H-indole-3-carboxylate

HRID 1054726Notes

Reaction equation

HRID 1054726 reaction equation
CC1(C)C(C)(C)OB([C:9]2[CH:14]=[CH:13][C:12]([C:15]3[C:16]([OH:21])=[CH:17][CH:18]=[CH:19][CH:20]=3)=[CH:11][CH:10]=2)O1.Br[C:24]1[CH:25]=[C:26]2[C:30](=[CH:31][C:32]=1[Cl:33])[NH:29][CH:28]=[C:27]2[C:34]([O:36][CH3:37])=[O:35].C(=O)([O-])[O-].[K+].[K+].S([O-])(O)(=O)=O.[Na+]>C(OCC)(=O)C.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].CCO.C1COCC1.C1(C)C=CC=CC=1>[Cl:33][C:32]1[CH:31]=[C:30]2[C:26]([C:27]([C:34]([O:36][CH3:37])=[O:35])=[CH:28][NH:29]2)=[CH:25][C:24]=1[C:9]1[CH:10]=[CH:11][C:12]([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=2[OH:21])=[CH:13][CH:14]=1

Participants

10

Reactant 4

HCID 11430Potassium CarbonateHCID 516919Sodium BisulfateHCID 592678134'-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-[1,1'-biphenyl]-2-olHCID 86698569methyl 5-bromo-6-chloro-1H-indole-3-carboxylate

Product 1

HCID 86698725methyl 6-chloro-5-(2'-hydroxybiphenyl-4-yl)-1H-indole-3-carboxylateYield 73%

Reagents, catalysts & solvents 5

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 702EthanolSolventHCID 1140TolueneSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
115 °C

Procedure

A glass tube was charged with 4′-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-[1,1′-biphenyl]-2-ol (86.2 mg, 0.29 mmol), methyl 5-bromo-6-chloro-1H-indole-3-carboxylate (84 mg, 0.29 mmol), toluene (1.2 mL), THF (0.6 mL), EtOH (0.6 mL), and 2.0 M potassium carbonate solution (0.6 mL, 1.2 mmol). Nitrogen was then bubbled through the mixture for 5 minutes then [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) (28 mg, 0.032 mmol) was added. The tube was sealed and heated to 115° C. for 2 hours. The reaction was cooled to room temperature, opened, and neutralized with 1.0 M sodium hydrogensulfate then diluted with ethyl acetate. The layers were separated and the aqueous extracted with ethyl acetate (×2). The combined organic layers were dried over sodium sulfate, filtered, and concentrated in vacuo. Flash column chromatography (20% to 100% ethyl acetate/heptane) was then used to to provide the title compound as a white solid (80 mg, 73% yield). MS (ES−) 376.1 (M−H). 1H NMR (500 MHz, DMSO-d6) δ 12.09 (br. s., 1 H), 9.60 (s, 1 H), 8.19 (s, 1 H), 7.98 (s, 1 H), 7.68 (s, 1 H), 7.65 (d, 2 H), 7.47 (d, 2 H), 7.34 (dd, 1 H), 7.19 (dt, 1 H), 6.98 (d, 1 H), 6.91 (dt, 1 H), 3.81 (s, 3 H).

Workup

  1. customNitrogen was then bubbled through the mixture for 5 minutes
  2. customThe tube was sealed
  3. temperatureThe reaction was cooled to room temperature
  4. customThe layers were separated
  5. extractionthe aqueous extracted with ethyl acetate (×2)
  6. dry with materialThe combined organic layers were dried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-0c96e6b23a824242acbe2923aeb0882b
Source dataset
uspto-grants-2016_07
Patent number
US09394285B2

Reaction notes

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