Indole → HCID 57655360, compound

HRID 717102Notes

Reaction equation

HRID 717102 reaction equation
[H-].[Na+].[NH:3]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[CH:5]=[CH:4]1.Br[CH2:13][C:14]1[CH:19]=[CH:18][C:17]([B:20]2[O:28][C:25]([CH3:27])([CH3:26])[C:22]([CH3:24])([CH3:23])[O:21]2)=[CH:16][CH:15]=1>CN(C=O)C.O>[CH3:26][C:25]1([CH3:27])[C:22]([CH3:23])([CH3:24])[O:21][B:20]([C:17]2[CH:16]=[CH:15][C:14]([CH2:13][N:3]3[C:11]4[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=4)[CH:5]=[CH:4]3)=[CH:19][CH:18]=2)[O:28]1

Participants

6

Reactant 3

HCID 798IndoleHCID 24758Sodium hydrideHCID 37345062-(4-(Bromomethyl)phenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane

Product 1

HCID 57655360HCID 57655360, compoundYield 20.5%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent3×

Procedure

To NaH (78 mg, 1.94 mmol) in anhydrous DMF (4 mL) under N2, at 0° C. was added indole (227 mg, 1.94 mmol) in anhydrous DMF (5 mL). The reaxtion mixture was maintained at this temperature for 10 min. 4-bromomethylphenylboronic acid pinacol ester (523 mg, 1.76 mmol) in anhydrous DMF (8 mL) was added and the reaction stirred at RT for 18 h. The reaction mixture was diluted with H2O and extracted with CH2Cl2 (×2). The organic phases were combined, washed with brine, dried (phase separation cartridge) and the solvent removed in vacuo. The crude material was purified by silica gel column chromatography eluting with isohexane and increasing the polarity to 5% EtOAc/isohexane. The compound was further purified by reverse phase preparative HPLC-MS to afford 1-[4-(4,4,5,5-Tetramethyl-[1,3,2]dioxaborolan-2-yl)-benzyl]-1H-indole as an off-white solid (120 mg, 10%).

Workup

  1. temperatureThe reaxtion mixture was maintained at this temperature for 10 min
  2. extractionextracted with CH2Cl2 (×2)
  3. washwashed with brine
  4. customdried
  5. custom(phase separation cartridge)
  6. customthe solvent removed in vacuo
  7. customThe crude material was purified by silica gel column chromatography
  8. washeluting with isohexane
  9. temperatureincreasing the polarity to 5% EtOAc/isohexane
  10. customThe compound was further purified by reverse phase preparative HPLC-MS

Sources & evidence

ORD record
ord-8f67a4f040d84d0a8453f9210823cc70
Source dataset
uspto-grants-2015_11
Patent number
US09193689B2

Reaction notes

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