Water → HCID 86698767, compound

HRID 338435Notes

Reaction equation

HRID 338435 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 2N 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-4ca624900ee84a59a60d91bc6285783f
Source dataset
uspto-grants-2014_11
Patent number
US08889730B2

Reaction notes

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