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

HRID 1178906Notes

Reaction equation

HRID 1178906 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-4fd79a99684e4282aaaad65ec6a8280a
Source dataset
uspto-grants-2007_10
Patent number
US07276516B2

Reaction notes

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