Sodium Carbonate → HCID 69299386, compound

HRID 2054599Notes

Reaction equation

HRID 2054599 reaction equation
[CH:1]1[C:9]2[C:8]3[CH:10]=[CH:11][CH:12]=[CH:13][C:7]=3[O:6][C:5]=2[C:4](B(O)O)=[CH:3][CH:2]=1.[CH3:17][O:18][C:19](=[O:42])[CH2:20][CH2:21][C:22]([C:24]1[C:32]2[C:27](=[CH:28][CH:29]=[C:30]([Cl:33])[CH:31]=2)[N:26]([CH2:34][C:35]2[CH:36]=[N:37][C:38](Cl)=[CH:39][CH:40]=2)[CH:25]=1)=[O:23].C(=O)([O-])[O-].[Na+].[Na+]>CO.C1(C)C=CC=CC=1.[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[CH3:17][O:18][C:19](=[O:42])[CH2:20][CH2:21][C:22]([C:24]1[C:32]2[C:27](=[CH:28][CH:29]=[C:30]([Cl:33])[CH:31]=2)[N:26]([CH2:34][C:35]2[CH:36]=[N:37][C:38]([C:4]3[C:5]4[O:6][C:7]5[CH:13]=[CH:12][CH:11]=[CH:10][C:8]=5[C:9]=4[CH:1]=[CH:2][CH:3]=3)=[CH:39][CH:40]=2)[CH:25]=1)=[O:23]

Participants

7

Reactant 3

HCID 10340Sodium CarbonateHCID 2734328Dibenzofuran-4-boronic acidHCID 86595728HCID 86595728, compound

Product 1

HCID 69299386HCID 69299386, compoundYield 82.1%

Reagents, catalysts & solvents 3

HCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 887MethanolSolventHCID 1140TolueneSolvent

Conditions

Temperature
90 °C

Procedure

A solution of dibenzofuran-4-boronic acid (422 mg, 1.98 mmol) in methanol (10 mL) was added to a stirred solution methyl-4-[5-chloro-1-(6-chloropyridin-3-ylmethyl)-1H-indol-3-yl]-4-oxo-butyrate (650 mg, 1.66 mmol) and tetrakis-(triphenylphosphine)-palladium(0) (72 mg, 5 mol %) in toluene (40 mL). 2N sodium carbonate (1.66 mL, 3.32 mmol) was added and the reaction was heated to 90° C. (oil bath temp.) for 2-3 hrs until complete (TLC control). The reaction mixture was cooled to room temperature and partitioned between water and diethyl ether. The phases were separated, the aqueous phase being further extracted with diethyl ether (2×30 mL). The combined extract was washed with water and brine. The ethereal solution was dried over anhydrous MgSO4, filtered and concentrated in vacuo to yield methyl-4-[5-chloro-1-(6-dibenzofuran-4-yl-pyridin-3-ylmethyl)-1H-indol-3-yl]-4-oxo-butyrate as a white solid (713 mg, 82%); Rf: 0.5 (50% ethyl acetate in heptane); 1H NMR (CDCl3, 300 MHz) δ 8.71 (1H, s, ArH), 8.41 (2H, m, ArH), 8.27 (1H, d, J=8 Hz, ArH), 8.00 (2H, m, ArH), 7.89 (2H, s, ArH), 7.44-7.58 (4H, m, ArH), 7.39 (2H, m, ArH), 5.43 (2H, s, CH2N), 3.71 (3H, s OMe), 3.21 (2H, t, J=7 Hz, CH2CO), 2.80 (2H, t, J=7 Hz, CH2CO); ESI-LCMS e/z calculated for C31H23ClN2O4 522.980, found 523 [M+H (35Cl)]+, 525 [M+H (37Cl)]+, 545 [M+Na (35Cl)]+, 547 [M+Na (37Cl)]+.

Workup

  1. temperatureThe reaction mixture was cooled to room temperature
  2. custompartitioned between water and diethyl ether
  3. customThe phases were separated
  4. extractionthe aqueous phase being further extracted with diethyl ether (2×30 mL)
  5. extractionThe combined extract
  6. washwas washed with water and brine
  7. dry with materialThe ethereal solution was dried over anhydrous MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-3bccd1ac2d244cff8f1b0b3cb1b53ea1
Source dataset
uspto-grants-2008_02
Patent number
US07329680B2

Reaction notes

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