Dichloromethane → HCID 68815060, compound

HRID 731026Notes

Reaction equation

HRID 731026 reaction equation
[CH2:1]([N:8]1[C:16]2[C:11](=[CH:12][C:13](Br)=[CH:14][CH:15]=2)[C:10]([CH3:18])=[C:9]1[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C([O-])([O-])=O.[K+].[K+].[CH3:31][O:32][C:33]1[CH:38]=[CH:37][C:36](B(O)O)=[CH:35][CH:34]=1.ClCCl>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]>[CH2:1]([N:8]1[C:16]2[C:11](=[CH:12][C:13]([C:36]3[CH:37]=[CH:38][C:33]([O:32][CH3:31])=[CH:34][CH:35]=3)=[CH:14][CH:15]=2)[C:10]([CH3:18])=[C:9]1[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

7

Reactant 4

HCID 6344DichloromethaneHCID 11430Potassium CarbonateHCID 201262(4-Methoxyphenyl)boronic acidHCID 68815040HCID 68815040, compound

Product 1

HCID 68815060HCID 68815060, compoundYield 119.5%

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 312751,4-DioxaneSolvent

Procedure

To a solution of 1-benzyl-5-bromo-3-methyl-2-phenyl-1H-indole (1.907 g, 5.068 mmol) in dioxane (51 ml) was added aqueous 2M K2CO3 (5.1 ml) followed by 4-methoxyphenylboronic acid (0.924 g, 6.082 mmol) and [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium (II) complex with dichloromethane (1:1) (0.083 g, 0.101 mmol). The mixture was stirred at RT for 0.75 hours, then warmed to ˜90° C. After heating for 18 hours, the reaction mixture was cooled and concentrated. The residue was partitioned between EtOAc (120 ml) and 1N HCl (30 ml). The layers were shaken, separated, and the organic layer washed with 1N HCl (2×20 ml) and brine (2×20 ml), dried over Na2SO4, filtered, concentrated, and dried to give a black residue (2.444 g). The residue was purified by flash column chromatography (silica), eluting with hexane, 0.5% and 1% EOAc/hexane, to give the product (1.223 g, 3.031 mmol, 60%) as an off-white solid, mp 117-122° C. 1H NMR (DMSO-d6) δ 2.26 (s, 3H), 3.79 (s, 3H), 5.32 (s, 2H), 6.85 (d, J=7.3 Hz, 2H), 7.00 (d, J=8.7 Hz, 2H), 7.15 (t, J=7.0 Hz, 1H), 7.20 (t, J=6.7 Hz, 2H), 7.35-7.44 (m, 5H), 7.49 (t, J=7.0 Hz, 2H), 7.62 (d, J=8.7 Hz, 2H), 7.75 (s, 1H); [ESI(+)], m/z 404 (M+H)+.

Workup

  1. temperaturewarmed to ˜90° C
  2. temperatureAfter heating for 18 hours
  3. temperaturethe reaction mixture was cooled
  4. concentrationconcentrated
  5. customThe residue was partitioned between EtOAc (120 ml) and 1N HCl (30 ml)
  6. stirringThe layers were shaken
  7. customseparated
  8. washthe organic layer washed with 1N HCl (2×20 ml) and brine (2×20 ml)
  9. dry with materialdried over Na2SO4
  10. filtrationfiltered
  11. concentrationconcentrated
  12. customdried

Sources & evidence

ORD record
ord-0b3415f176b04585b19389262b7887d7
Source dataset
uspto-grants-2009_09
Patent number
US07582773B2

Reaction notes

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