Potassium Phosphate, Tribasic → Potassium Phosphate, Tribasic

HRID 1054705Notes

Reaction equation

HRID 1054705 reaction equation
[Cl:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([C:11]([O:13][CH3:14])=[O:12])=[CH:7][NH:8]2)=[CH:4][C:3]=1B1OCC(C)(C)CO1.[Br:23][C:24]1[CH:32]=[CH:31][C:27]2[CH2:28][CH2:29][O:30][C:26]=2[CH:25]=1.[O-:33][P:34]([O-:37])([O-:36])=[O:35].[K+:38].[K+].[K+]>O1CCOCC1.O.[Pd](Cl)Cl.C(P(C(C)(C)C)[C-]1C=CC=C1)(C)(C)C.[C-]1(P(C(C)(C)C)C(C)(C)C)C=CC=C1.[Fe+2]>[Br:23][C:24]1[CH:32]=[CH:31][C:27]2[CH2:28][CH2:29][O:30][C:26]=2[CH:25]=1.[O-:35][P:34]([O-:37])([O-:36])=[O:33].[K+:38].[K+:38].[K+:38].[Cl:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([C:11]([O:13][CH3:14])=[O:12])=[CH:7][NH:8]2)=[CH:4][C:3]=1[C:24]1[CH:32]=[CH:31][C:27]2[CH2:28][CH2:29][O:30][C:26]=2[CH:25]=1

Participants

9

Reactant 3

HCID 62657Potassium Phosphate, TribasicHCID 112526166-Bromo-2,3-dihydro-1-benzofuranHCID 86698665methyl 6-chloro-5-(5,5-dimethyl-1,3,2-dioxaborinan-2-yl)-1H-indole-3-carboxylate2×

Product 3

HCID 62657Potassium Phosphate, TribasicHCID 112526166-Bromo-2,3-dihydro-1-benzofuranHCID 86698703methyl 6-chloro-5-(2,3-dihydrobenzofuran-6-yl)-1H-indole-3-carboxylate

Reagents, catalysts & solvents 3

HCID 178454861HCID 178454861, compoundCatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent4×

Conditions

Temperature
120 °C

Procedure

A 0.25 M solution of 6-bromo-2,3-dihydrobenzofuran was prepared in dioxane. A 0.30 M solution of methyl 6-chloro-5-(5,5-dimethyl-1,3,2-dioxaborinan-2-yl)-1H-indole-3-carboxylate was also prepared in dioxane. Lastly, a 1.00 M solution of K3PO4 was prepared in water. In a vial was added 400 uL of the 0.30 M dioxane solution of 6-bromo-2,3-dihydrobenzofuran (100 umol, 1.00 eq). 400 uL of the 0.25 M dioxane solution of methyl 6-chloro-5-(5,5-dimethyl-1,3,2-dioxaborinan-2-yl)-1H-indole-3-carboxylate (120 umol, 1.20 eq) was then added followed by the addition of 200 uL of the 1.00 M aqueous solution of K3PO4 (200 umol, 2.00 eq). Under nitrogen atmosphere was added (1,1′-bis(di-tert-butylphosphino)ferrocene palladium dichloride (3.9 mg, 6.0 umol, 0.06 eq). The vial was caped and shook for 2 hours at 120° C. The reaction was filtered and concentrated by Speedvac. The residue was washed with saturated aqueous sodium bicarbonate and extracted with ethyl acetate (1 mL, 3×). The organic layer was collected and dried over anhydrous sodium sulfate, filtered, and concentrated to give crude methyl 6-chloro-5-(2,3-dihydrobenzofuran-6-yl)-1H-indole-3-carboxylate. To the crude intermediate was added anhydrous tetrahydrofuran (1.5 mL) followed by Me3SiOK (128 mg, 1000 umol, 10.0 eq). The vial was capped and shaken at 80° C. for 16 hours. The reaction was concentrated by Speedvac and the residue was purified by preparative HPLC to provide the title compound. MS (ES+) 314 (M+H)+. Retention time: 2.56 min. Column: Agella Venusil ASB dC18 150×21.2 mm, 5 μm. Modifier: TFA 0.225%. Gradient: 66% H2O/34% MeCN linear to 36% H2O/64% MeCN over 10.0 min., HOLD at 100% MeCN to 1.0 min. Flow: 30.0 mL/min.

Workup

  1. customThe vial was caped
  2. filtrationThe reaction was filtered
  3. concentrationconcentrated by Speedvac
  4. washThe residue was washed with saturated aqueous sodium bicarbonate
  5. extractionextracted with ethyl acetate (1 mL, 3×)
  6. customThe organic layer was collected
  7. dry with materialdried over anhydrous sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated

Sources & evidence

ORD record
ord-639cd24ca657485eb1fd767930817fc4
Source dataset
uspto-grants-2016_07
Patent number
US09394285B2

Reaction notes

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