Methyl 4-(bromomethyl)-3-methoxybenzoate → methyl 4-[5-[N-(3-methylbutyl)carbamoyl]indol-3-ylmethyl]-3-methoxybenzoate

HRID 728681Notes

Reaction equation

HRID 728681 reaction equation
[CH3:1][CH:2]([CH3:17])[CH2:3][CH2:4][NH:5][C:6]([C:8]1[CH:9]=[C:10]2[C:14](=[CH:15][CH:16]=1)[NH:13][CH:12]=[CH:11]2)=[O:7].Br[CH2:19][C:20]1[CH:29]=[CH:28][C:23]([C:24]([O:26][CH3:27])=[O:25])=[CH:22][C:21]=1[O:30][CH3:31]>C1(C)C=CC=CC=1.C(OCC)(=O)C.[Ag-]=O>[CH3:1][CH:2]([CH3:17])[CH2:3][CH2:4][NH:5][C:6]([C:8]1[CH:9]=[C:10]2[C:14](=[CH:15][CH:16]=1)[NH:13][CH:12]=[C:11]2[CH2:19][C:20]1[CH:29]=[CH:28][C:23]([C:24]([O:26][CH3:27])=[O:25])=[CH:22][C:21]=1[O:30][CH3:31])=[O:7]

Participants

6

Reactant 2

HCID 2759828Methyl 4-(bromomethyl)-3-methoxybenzoateHCID 99914665-[N-(3-methylbutyl)carbamoyl]-indole

Product 1

HCID 10364106methyl 4-[5-[N-(3-methylbutyl)carbamoyl]indol-3-ylmethyl]-3-methoxybenzoateYield 13%

Reagents, catalysts & solvents 3

HCID 178418778HCID 178418778, compoundCatalystHCID 1140TolueneSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

Silver(I) oxide (4.92 g) was added to a solution of indole (F) (2.05 g) in toluene (15 ml). The mixture was protected from light, stirred, and heated to reflux under an atmosphere of nitrogen for 24 hours. A solution of methyl 4-bromomethyl-3-methoxybenzoate (B) (2.31 g) in toluene (5 ml) was added, and stirring was continued at 95° C. for 4 hours. The mixture was then diluted with ethyl acetate and filtered. The filtrate was evaporated to give an amber gum which was purified by flash chromatography on silica gel (862 ml), eluting with 1:99 v/v methanol:chloroform to give (E) (0.47 g, 13%) as a white foam; partial NMR (80 MHz, CDCl3): 0.92[d, 6H, CH(CH3)2], 3.40(q, 2H, NCH2), 3.87(s, 3H, OCH3), 4.09(s, 2H, ArCH2), 6.18(br t, 1H, CONH), 7.98(br s, 1H, H4 -indole), 8.84(br s, 1; H, NH).

Workup

  1. temperatureheated
  2. temperatureto reflux under an atmosphere of nitrogen for 24 hours
  3. stirringstirring
  4. filtrationfiltered
  5. customThe filtrate was evaporated
  6. customto give an amber gum which
  7. customwas purified by flash chromatography on silica gel (862 ml)
  8. washeluting with 1:99 v/v methanol

Sources & evidence

ORD record
ord-1aecf0972f2d4a63ba3cefa1d2bfc937
Source dataset
uspto-grants-1991_09
Patent number
US05049679

Reaction notes

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