Tetrahydrofuran → 3-Morpholin-4-yl-1-triisopropylsilanyl-1H-indole

HRID 736969Notes

Reaction equation

HRID 736969 reaction equation
Br[C:2]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[N:4]([Si:11]([CH:18]([CH3:20])[CH3:19])([CH:15]([CH3:17])[CH3:16])[CH:12]([CH3:14])[CH3:13])[CH:3]=1.[NH:21]1[CH2:26][CH2:25][O:24][CH2:23][CH2:22]1.C[Si]([N-][Si](C)(C)C)(C)C.[Li+].C1COCC1>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C(Cl)(Cl)Cl.[Pd].[Pd].C1(P(C2CCCCC2)C2C=CC=CC=2C2C=CC=CC=2N(C)C)CCCCC1>[N:21]1([C:2]2[C:10]3[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=3)[N:4]([Si:11]([CH:18]([CH3:20])[CH3:19])([CH:15]([CH3:17])[CH3:16])[CH:12]([CH3:14])[CH3:13])[CH:3]=2)[CH2:26][CH2:25][O:24][CH2:23][CH2:22]1

Participants

7

Reactant 4

HCID 8028TetrahydrofuranHCID 8083MorpholineHCID 2733832Lithium HexamethyldisilazideHCID 109917693-Bromo-1-(triisopropylsilyl)indole

Product 1

HCID 589751763-Morpholin-4-yl-1-triisopropylsilanyl-1H-indoleYield 60%

Reagents, catalysts & solvents 2

HCID 27342172-(Dicyclohexylphosphino)-2'-(dimethylamino)biphenylCatalystHCID 11029508Palladium, tris[mu-[(1,2-eta:4,5-eta)-(1E,4E)-1,5-diphenyl-1,4-pentadien-3-one]]di-, compd. with trichloromethane (1:1)Catalyst

Conditions

Temperature
65 °C

Procedure

Combine 3-bromo-1-triisopropylsilanyl-1H-indole (0.33 g, 0.94 mmol), morpholine (0.10 mL, 1.15 mmol), 2-dicyclohexylphosphino-2′-(N,N-dimethylamino)biphenyl (0.012 g, 0.03 mmol), and tris(dibenzylideneacetone)dipalladium(0) chloroform adduct (0.012 g, 0.01 mmol) in a pressure tube. Add 1N solution of lithium bis(trimethylsilyl)amide in THF (2.00 mL, 2.00 mmol), flush tube with nitrogen gas, and close the tube. Stir at 65° C. for 18 h, cool to room temperature, dilute with water, and extract with EtOAc. Wash EtOAc layer with water, brine, dry (Na2SO4), and concentrate under vacuum. Purify the residue by flash chromatography using 0 to 50% of EtOAc in hexanes to give the title compound (0.20 g 60%): MS (ES) 359.1 (M+1)+.

Workup

  1. customflush tube with nitrogen gas
  2. customclose the tube
  3. temperaturecool to room temperature
  4. additiondilute with water
  5. extractionextract with EtOAc
  6. dry with materialWash EtOAc layer with water, brine, dry (Na2SO4)
  7. concentrationconcentrate under vacuum
  8. customPurify the residue by flash chromatography

Sources & evidence

ORD record
ord-39272f2a039c4af58642dca180712093
Source dataset
uspto-grants-2009_09
Patent number
US07595339B2

Reaction notes

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