Potassium Carbonate → 6-Chloro-5-(2'-hydroxy-[1,1'-biphenyl]-4-yl)-1H-indole-3-sulfonic acid

HRID 338498Notes

Reaction equation

HRID 338498 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][C:10]=1[Cl:11])[NH:7][CH:6]=[C:5]2[S:12]([OH:15])(=[O:14])=[O:13].CC1(C)C(C)(C)OB([C:24]2[CH:29]=[CH:28][C:27]([C:30]3[C:31]([OH:36])=[CH:32][CH:33]=[CH:34][CH:35]=3)=[CH:26][CH:25]=2)O1.C(=O)([O-])[O-].[K+].[K+]>CCO.O.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]>[Cl:11][C:10]1[CH:9]=[C:8]2[C:4]([C:5]([S:12]([OH:15])(=[O:14])=[O:13])=[CH:6][NH:7]2)=[CH:3][C:2]=1[C:24]1[CH:25]=[CH:26][C:27]([C:30]2[CH:35]=[CH:34][CH:33]=[CH:32][C:31]=2[OH:36])=[CH:28][CH:29]=1

Participants

7

Reactant 3

HCID 11430Potassium CarbonateHCID 592678134'-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-[1,1'-biphenyl]-2-olHCID 866988345-bromo-6-chloro-1H-indole-3-sulfonic acid

Product 1

HCID 866988356-Chloro-5-(2'-hydroxy-[1,1'-biphenyl]-4-yl)-1H-indole-3-sulfonic acidYield 2%

Reagents, catalysts & solvents 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 702EthanolSolventHCID 962WaterSolvent

Conditions

Temperature
130 °C

Procedure

A mixture of 5-bromo-6-chloro-1H-indole (300 mg, 1.30 mmol) and sulfur trioxide pyridine complex (622 mg, 3.91 mmol) in pyridine (2 mL) was sealed in a pressure tube and heated to 100° C. for 48 hours. The reaction mixture was concentrated in vacuo to provide 5-bromo-6-chloro-1H-indole-3-sulfonic acid as a pyridinium salt, which was used directly in the next step without further purification. A mixture of 5-bromo-6-chloro-1H-indole-3-sulfonic acid (100 mg, 0.32 mmol), 4′-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-biphenyl-2-ol (114 mg, 0.39 mmol), 2N aqueous potassium carbonate solution (0.64 mL, 1.29 mmol) and [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) (13.0 mg, 0.016 mmol) in EtOH (5 mL) was sealed and heated to 130° C. for 2 hours. The reaction mixture was diluted with water (10 mL) and washed with EtOAc (2×10 mL). The aqueous layer was concentrated in vacuo and purified by reversed phase HPLC (Column: Waters Sunfire C18 19×100, 5 μm; Mobile phase A: 0.05% TFA in water (v/v); Mobile phase B: 0.05% TFA in MeCN (v/v); HOLD at 100.0% H2O/0.0% MeCN for 1.0 min. 100.0% H2O/0.0% MeCN linear to 5.0% H2O/95.0% MeCN in 6.75 min, linear to 0% H2O/100% MeCN to 7.0 min. HOLD at 0% H2O/100% MeCN from 7.0 to 8.0 min. Flow: 30 mL/min.) to provide the title compound (2.3 mg, 2%). MS (ES−) 398.0 (M−H)+. Retention time=2.28 minutes (Waters Atlantis dC18 4.6×50, 5 μm; Mobile phase A: 0.05% TFA in water (v/v); Mobile phase B: 0.05% TFA in MeCN (v/v); Gradient: 95:5 A:B linear to 5:95 A:B in 4.0 min, hold at 5:95 A:B to 5.0 min. Flow: 2 mL/min).

Workup

  1. customwas used directly in the next step without further purification
  2. customwas sealed
  3. washwashed with EtOAc (2×10 mL)
  4. concentrationThe aqueous layer was concentrated in vacuo
  5. custompurified by reversed phase HPLC (Column: Waters Sunfire C18 19×100, 5 μm; Mobile phase A: 0.05% TFA in water (v/v); Mobile phase B: 0.05% TFA in MeCN (v/v); HOLD at 100.0% H2O/0.0% MeCN for 1.0 min. 100.0% H2O/0.0% MeCN linear to 5.0% H2O/95.0% MeCN in 6.75 min, linear to 0% H2O/100% MeCN to 7.0 min. HOLD at 0% H2O/100% MeCN from 7.0 to 8.0 min. Flow: 30 mL/min.)

Sources & evidence

ORD record
ord-5c46f88b017d480cae9d52dbb31b90ba
Source dataset
uspto-grants-2014_11
Patent number
US08889730B2

Reaction notes

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