Sodium Carbonate → HCID 68614711, compound

HRID 273351Notes

Reaction equation

HRID 273351 reaction equation
BrC(=C)C[N:4]1[C:12]2[C:7](=[CH:8][CH:9]=[C:10]([C:13]([O:15][CH3:16])=[O:14])[CH:11]=2)[C:6]([CH:17]2[CH2:22][CH2:21][CH2:20][CH2:19][CH2:18]2)=[C:5]1[C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][C:24]=1[CH:29]=[CH2:30].[O:32]1[CH:36]=[CH:35][C:34](B(O)O)=[CH:33]1.[Li+].[Cl-].C(=O)([O-])[O-].[Na+].[Na+]>C(O)C.C1(C)C=CC=CC=1.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH:17]1([C:6]2[C:7]3[C:12](=[CH:11][C:10]([C:13]([O:15][CH3:16])=[O:14])=[CH:9][CH:8]=3)[N:4]([C:34]3[CH:35]=[CH:36][O:32][CH:33]=3)[C:5]=2[C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][C:24]=2[CH:29]=[CH2:30])[CH2:22][CH2:21][CH2:20][CH2:19][CH2:18]1

Participants

8

Reactant 4

HCID 10340Sodium CarbonateHCID 433294Lithium ChlorideHCID 2734358Furan-3-boronic acidHCID 58940682HCID 58940682, compound

Product 1

HCID 68614711HCID 68614711, compoundYield 40.6%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 702EthanolSolventHCID 1140TolueneSolvent

Procedure

Step 1: Sodium hydride (44 mg of 95%, 1.74 mmol) was added to an ice cold solution of methyl 3-cyclohexyl-2-(2-vinylphenyl) 1H-indole-6-carboxylate (0.500 mg, 1.34 mmol) in THF (6 mL). When the evolution of hydrogen subsided, 2,3-dibromoprop-1-ene (402 mg, 2.01 mmol) was added in a single portion. Stirring was continued at 0° C. for 2 hr and then at 22° C. for 24 hr. The solution was concentrated and the residue chromatographed on SiO2 with petroleum ether-ethyl acetate (10:1 H using the flash technique to afford methyl 1-(2-bromoallyl)-3-cyclohexyl-2-(2-vinylphenyl)-1H-indole-6-carboxylate (285 mg, 44.5%) as a gummy solid. MS m/z 479 (MH+). Step 2: Tetrakis(triphenylphosphine)palladium(0 H (38 mg, 0.033 mmol) was added to a stirred and degassed mixture of methyl 1-(2-bromoallyl)-3-cyclohexyl-2-(2-vinylphenyl)-1H-indole-6-carboxylate (157 mg, 0.33 mmol), 3-furylboronic acid (54.5 mg, 0.49 mmol), LiCl (55 mg, 0.66 mmol) in ethanol (2 mL) and toluene (2 mL) containing 1M aqueous sodium carbonate (0.82 mL, 0.82 mmol). The mixture was heated under reflux for 1 hr, cooled and partitioned between ethyl acetate and water. The organic layer was washed (water, brine), dried over sopdium sulfate and concentrated. The crude product was purified on a silicic acid thick layer plate. The plate was eluted with hexanes-ethyl acetate (10:1 H to provide methyl 3-cyclohexyl-1-(furan-3-yl)-2-(2-vinylphenyl)-1H-indole-6-carboxylate as a gum (57 mg, 37%). MS m/z 466 (MH+); 1H NMR (500 MHz, CHLOROFORM-D) δ ppm 1.15-1.89 (m, 10 H) 2.42-2.53 (m, 1 H) 3.91 (s, 3 H) 4.25 (s, 1 H) 4.48 (d, J=17.40 Hz, 1 H) 4.82 (d, J=17.40 Hz, 1 H) 4.82 (d, J=17.40 Hz, 1 H). 5.09-5.17 (m, 2 H) 5.69 (d, J=17.70 Hz, 1 H) 6.34-6.47 (m, 2 H) 7.18-7.23 (m, 2 H) 7.28 (t, J=7.93 Hz, 1 H) 7.32 (t, J=1.68 Hz, 1 H) 7.42 (t, J=7.63 Hz, 1 H) 7.69 (d, J=7.63 Hz, 1 H) 7.79-7.85 (m, 2 H) 8.00 (s, 1 H). Step 3: Grubb's second generation catalyst (10 mg) was added to a solution of methyl 3-cyclohexyl-1-(furan-3-yl)-2-(2-vinylphenyl)-1H-indole-6-carboxylate (47 mg) in methylene chloride (8 mL). The solution was stirred under reflux for 18 hr and concentrated to dryness The residue was purified on a silicic acid preparative plate. The plate was eluted with hexanes-ethyl acetate (10:1 H. The product containing band was extracted and the extract was concentrated. Purification on a second thick layer plate afforded 13-cyclohexyl-6-(furan-3-yl)-7H-indolo{2,1-a][2]benzazepine-10-carboxylate as a golden solid (17 mg, 39%). MS m/z 438 (MH+); 1H NMR (300 MHz, CHLOROFORM-D) δ ppm 1.11-2.16 (m, 10H) 2.78-2.95 (m, 1 H) 3.94 (s, 3 H) 4.34-4.49 (m, 1 H) 5.00-5.15 (m, 1 H) 6.60 (s, 1 H) 6.93 (s, 1 H) 7.38-7.45 (m, 4 H) 7.55 (d, J=8.42 Hz, 1 H) 7.70 (dd, J=8.42, 1.46 Hz, 1 H) 7.81-7.88 (m, 2 H) 8.17 (s, 1 H). Step 4: A mixture of the preceding ester (17 mg) in THF (250 μL), methanol (250 μL), and 1.0 N NaOH (200 μL) was heated at 100° C. on a microwave apparatus for 15 min. The resulting solution was cooled and acidified with dilute HCl to precipitate the titled acid as a golden solid. MS m/z 424 (MH+).

Workup

  1. customdegassed
  2. temperatureThe mixture was heated
  3. temperatureunder reflux for 1 hr
  4. temperaturecooled
  5. custompartitioned between ethyl acetate and water
  6. washThe organic layer was washed (water, brine)
  7. dry with materialdried over sopdium sulfate
  8. concentrationconcentrated
  9. customThe crude product was purified on a silicic acid thick layer plate
  10. washThe plate was eluted with hexanes-ethyl acetate (10:1 H

Sources & evidence

ORD record
ord-59d456224fa8416b9094d79753fd02d9
Source dataset
uspto-grants-2008_11
Patent number
US07456165B2

Reaction notes

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