Potassium Carbonate → HCID 86698836, compound

HRID 338499Notes

Reaction equation

HRID 338499 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([CH:8]2[CH2:13][CH2:12][O:11][CH2:10][CH2:9]2)=[CH:4][CH:3]=1.CC1(C)COB(B2OCC(C)(C)CO2)OC1.C([O-])(=O)C.[K+].Br[C:36]1[CH:37]=[C:38]2[C:42](=[CH:43][C:44]=1[Cl:45])[NH:41][CH:40]=[C:39]2[S:46]([OH:49])(=[O:48])=[O:47].C(=O)([O-])[O-].[K+].[K+]>O1CCOCC1.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].CCO>[Cl:45][C:44]1[CH:43]=[C:42]2[C:38]([C:39]([S:46]([OH:49])(=[O:48])=[O:47])=[CH:40][NH:41]2)=[CH:37][C:36]=1[C:2]1[CH:7]=[CH:6][C:5]([CH:8]2[CH2:13][CH2:12][O:11][CH2:10][CH2:9]2)=[CH:4][CH:3]=1

Participants

10

Reactant 5

HCID 11430Potassium CarbonateHCID 517044Potassium AcetateHCID 2734316Bis(neopentyl glycolato)diboronHCID 198177774-(4-Bromophenyl)oxaneHCID 866988345-bromo-6-chloro-1H-indole-3-sulfonic acid

Product 1

HCID 86698836HCID 86698836, compoundYield 3.3%

Reagents, catalysts & solvents 4

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)Catalyst2×HCID 702EthanolSolventHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °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 4-(4-bromophenyl)tetrahydropyran (77.0 mg, 0.32 mmol), 5,5,5′,5′-tetramethyl-2,2′-bi-1,3,2-dioxaborinane (121 mg, 0.35 mmol), potassium acetate (95.0 mg, 0.97 mmol), and [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) (13.0 mg, 0.016 mmol) in 1,4-dioxane (1 mL) was sealed and heated to 100° C. for 1 hour. To the mixture was added the above freshly prepared 5-bromo-6-chloro-1H-indole-3-sulfonic acid (100 mg, 0.32 mmol), [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) (13.0 mg, 0.016 mmol), 2N aqueous potassium carbonate solution (0.65 mL, 1.30 mmol) and EtOH (5 mL). The reaction mixture was sealed and heated to 130° C. for 1 hour. The reaction mixture was diluted with water (10 mL), acidified to pH 2 and washed with EtOAc (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 (4.1 mg, 3%). MS (ES−) 390.0 (M−H)+. Retention time=2.12 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. customThe reaction mixture was sealed
  4. temperatureheated to 130° C. for 1 hour
  5. washwashed with EtOAc (10 mL)
  6. concentrationThe aqueous layer was concentrated in vacuo
  7. 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-e1a8b1edebcd46e085d09d5c9423bc86
Source dataset
uspto-grants-2014_11
Patent number
US08889730B2

Reaction notes

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