Water → HCID 86698767, compound

HRID 1054777Notes

Reaction equation

HRID 1054777 reaction equation
Br[C:2]1[CH:13]=[CH:12][C:5]2[O:6][C@H:7]([CH2:10][OH:11])[CH2:8][O:9][C:4]=2[CH:3]=1.[Cl:14][C:15]1[CH:23]=[C:22]2[C:18]([CH:19]=[CH:20][NH:21]2)=[CH:17][C:16]=1B1OCC(C)(C)CO1.[C:32](=O)([O-])[O-:33].[K+].[K+].O>CN(C=O)C.O1CCOCC1.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].C(Cl)Cl>[Cl:14][C:15]1[CH:23]=[C:22]2[C:18]([C:19]([CH:32]=[O:33])=[CH:20][NH:21]2)=[CH:17][C:16]=1[C:2]1[CH:13]=[CH:12][C:5]2[O:6][C@H:7]([CH2:10][OH:11])[CH2:8][O:9][C:4]=2[CH:3]=1

Participants

9

Reactant 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 46942285[(2R)-6-Bromo-2,3-dihydro-1,4-benzodioxin-2-yl]methanolHCID 866987336-chloro-5-(5,5-dimethyl-1,3,2-dioxaborinan-2-yl)-1H-indole

Product 1

HCID 86698767HCID 86698767, compoundYield 141.9%

Reagents, catalysts & solvents 4

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolventHCID 312751,4-DioxaneSolvent

Procedure

A mixture of [(2R)-6-bromo-2,3-dihydro-1,4-benzodioxin-2-yl]methanol (0.54 g, 2.05 mmol) (which can be prepared as in Biorg. Med. Chem. 2007, 15, 4048.), 6-chloro-5-(5,5-dimethyl-1,3,2-dioxaborinan-2-yl)-1H-indole (0.52 g, 4.06 mmol) in DMF (4 mL) and dioxane (4 mL) was stirred at room temperature for 30 min. under N2. Pd(dppf)Cl2 (100 mg, 0.137 mmol) and 2 N potassium carbonate (10 mL, 20 mmol) was added. The resulting mixture was stirred for 30 min. at 90° C. under N2. TLC showed the reaction was complete. Water (50 mL) and methylene chloride (50 mL) was added. The aqueous layer was extracted with methylene chloride (30 mL×3). The combined organic layer was dried over sodium sulfate, filtered and evaporated to give the title compound (1 g) which was used in the next step without further purification.

Workup

  1. stirringThe resulting mixture was stirred for 30 min. at 90° C. under N2
  2. extractionThe aqueous layer was extracted with methylene chloride (30 mL×3)
  3. dry with materialThe combined organic layer was dried over sodium sulfate
  4. filtrationfiltered
  5. customevaporated

Sources & evidence

ORD record
ord-2e8fa3c00ff745cda30570598101ac54
Source dataset
uspto-grants-2016_07
Patent number
US09394285B2

Reaction notes

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