Methylamine → 4-Bromo-2-(p-chlorophenyl)-1-(ethoxymethyl)-N-methyl-5-(trifluoromethyl)pyrrole-3-thiocarboxamide

HRID 274743Notes

Reaction equation

HRID 274743 reaction equation
C(OC(Cl)=O)C(C)C.[Br:9][C:10]1[C:11]([C:30](O)=O)=[C:12]([C:23]2[CH:28]=[CH:27][C:26]([Cl:29])=[CH:25][CH:24]=2)[N:13]([CH2:19][O:20][CH2:21][CH3:22])[C:14]=1[C:15]([F:18])([F:17])[F:16].C([N:35]([CH2:38]C)CC)C.CN.COC1C=CC(P2(=S)SP(=S)(C3C=CC(OC)=CC=3)[S:51]2)=CC=1>O1CCCC1.C(OCC)C.O>[Br:9][C:10]1[C:11]([C:30](=[S:51])[NH:35][CH3:38])=[C:12]([C:23]2[CH:28]=[CH:27][C:26]([Cl:29])=[CH:25][CH:24]=2)[N:13]([CH2:19][O:20][CH2:21][CH3:22])[C:14]=1[C:15]([F:18])([F:17])[F:16]

Participants

8

Reactant 5

HCID 6329MethylamineHCID 8471TriethylamineHCID 62365Isobutyl chloroformateHCID 87949Lawesson's reagentHCID 200936204-Bromo-2-(p-chlorophenyl)-1-(ethoxymethyl)-5-(trifluoromethyl)pyrrole-3-carboxylic acid

Product 1

HCID 200936244-Bromo-2-(p-chlorophenyl)-1-(ethoxymethyl)-N-methyl-5-(trifluoromethyl)pyrrole-3-thiocarboxamideYield 65.8%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 21584184Diethylether waterSolvent

Conditions

Temperature
0 °C

Procedure

Isobutylchloroformate (0.3 mL, 2.3 mmol) is added to a mixture of 4-bromo-2-(p-chlorophenyl)-1-(ethoxymethyl)-5-(trifluoromethyl)pyrrole-3-carboxylic acid (0.83 g, 2 mmol) and triethylamine (0.33 mL, 2.3 mmol) in tetrahydrofuran at 0° C. The mixture is stirred for 1 hour at 0° C., treated with a 6 wt/wt % methylamine solution (10.6 g, 20 mmol), stirred at room temperature for 2 hours and diluted with a diethyl ether/water mixture. The organic phase is separated, dried over anhydrous Na2SO4, concentrated in vacuo, diluted with toluene and concentrated in vacuo to obtain a liquid. A mixture of the liquid in tetrahydrofuran is treated with 2,4-bis(4-methoxyphenyl)-1,3-dithia-2,4-diphosphetane-2,4-disulfide (0.40 g, 1 mmol), heated at reflux for 2 hours, concentrated in vacuo and chromatographed on silica gel with a 4:1 hexane/ethyl acetate mixture to obtain the title product as a yellow gum (0.3 g) which is identified by 1H and 13C NMR spectral analyses.

Workup

  1. stirringstirred at room temperature for 2 hours
  2. customThe organic phase is separated
  3. dry with materialdried over anhydrous Na2SO4
  4. concentrationconcentrated in vacuo
  5. additiondiluted with toluene
  6. concentrationconcentrated in vacuo
  7. customto obtain a liquid
  8. temperatureheated
  9. temperatureat reflux for 2 hours
  10. concentrationconcentrated in vacuo
  11. customchromatographed on silica gel with a 4:1 hexane/ethyl acetate mixture

Sources & evidence

ORD record
ord-131ea53db42c4ca59dcd5ea5f6332fc0
Source dataset
uspto-grants-1995_02
Patent number
US05389669

Reaction notes

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