Dichloromethane → HCID 66854719, compound

HRID 1406405Notes

Reaction equation

HRID 1406405 reaction equation
[CH2:1]([O:3][C:4]([C:6]1[CH:11]=[C:10](I)[C:9](=[O:13])[N:8]([CH2:14][O:15][CH2:16][CH2:17][Si:18]([CH3:21])([CH3:20])[CH3:19])[C:7]=1[CH3:22])=[O:5])[CH3:2].C(=O)([O-])[O-].[K+].[K+].C(O[C:34]([N:36]1[C:44]2[C:39](=[CH:40][CH:41]=[CH:42][CH:43]=2)[CH:38]=[C:37]1B(O)O)=O)(C)(C)C.ClCCl>C1(P(C2C=CC=CC=2)[C-]2C=CC=C2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2].Cl[Pd]Cl.O.O1CCCC1>[CH2:1]([O:3][C:4]([C:6]1[CH:11]=[C:10]([C:37]2[N:36]([CH3:34])[C:44]3[C:39]([CH:38]=2)=[CH:40][CH:41]=[CH:42][CH:43]=3)[C:9](=[O:13])[N:8]([CH2:14][O:15][CH2:16][CH2:17][Si:18]([CH3:21])([CH3:20])[CH3:19])[C:7]=1[CH3:22])=[O:5])[CH3:2]

Participants

9

Reactant 4

HCID 6344DichloromethaneHCID 11430Potassium CarbonateHCID 27733021-(tert-Butoxycarbonyl)indole-2-boronic Acid (contains varying amounts of Anhydride)HCID 58117291HCID 58117291, compound2×

Product 1

HCID 66854719HCID 66854719, compound

Reagents, catalysts & solvents 4

HCID 24290Palladium ChlorideCatalystHCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)CatalystHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
60 °C

Procedure

A microwave vial (20 mL) was charged with intermediate (5d), 5-iodo-methyl-6-oxo-1-(2-trimethylsilanyl-ethoxymethyl)-1,6-dihydro-pyridine-3-carboxylic acid ethyl ester (0.87 g, 1.99 mmol), potassium carbonate (0.825 g, 5.97 mmol), 1-(tert-butoxycarbonyl) indole-2-boronic acid (0.624 g, 2.39 mmol), [1,1′-Bis(diphenylphosphino)ferrocene)]dichloropalladium(II), complex with dichloromethane (0.082 g, 5 mol %), tetrahydrofuran (14 mL) and water (2.3 mL). The contents of the vial were degassed and then heated at 60° C. for 1 hour under microwave irradiation. After cooling, the reaction mixture was partitioned between brine (50 mL) and ethyl acetate (50 mL). The organic layer was separated, dried (Na2SO4) and concentrated in vacuo. The resultant crude product was purified by flash chromatography on SiO2 with hexane—15% ethyl acetate/hexane (gradient) to afford the title compound as a yellow foam, 1.02 g, 97%.

Workup

  1. customThe contents of the vial were degassed
  2. temperatureAfter cooling
  3. customthe reaction mixture was partitioned between brine (50 mL) and ethyl acetate (50 mL)
  4. customThe organic layer was separated
  5. dry with materialdried (Na2SO4)
  6. concentrationconcentrated in vacuo
  7. customThe resultant crude product was purified by flash chromatography on SiO2 with hexane—15% ethyl acetate/hexane (gradient)

Sources & evidence

ORD record
ord-492e087285fa45dc8e63bb86617fbdff
Source dataset
uspto-grants-2014_12
Patent number
US08916591B2

Reaction notes

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