N,N,N',N'-Tetramethylethylenediamine → HCID 178503125, compound

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Reaction Conditions

Reaction Steps

Under an atmosphere of nitrogen, 1.6M n-butyl lithium in hexane (30 ml, 0.048 mole) was added dropwise to a solution of 1-(1-ethoxyethyl)-4-(4-fluorophenyl)-5-(4-methylthiophenyl)-1H-imidazole (10.0 g, 0.028 mole) and N,N,N',N'-tetramethylethylenediamine (3.9 g, 0.0336 mole) in tetrahydrofuran (150 ml) at -78° C. The mixture was stirred for 15 minutes at -78° C. and then N-(trimethylsilyl)hexafluoroacetone imine (11.0 g, 0.046 mole) was added dropwise at -78° C. The mixture was stirred for one hour at -78° C. and then allowed to warm to 0° C. A saturated aqueous solution of sodium bicarbonate (100 ml) was added dropwise while allowing the reaction mixture to warm to room temperature. The organic phase was separated and solvent removed in vacuo. Hydrochloric acid (2N; 100 ml) and ethanol (200 ml) were added to the residue and the mixture stirred overnight at room temperature. Ethanol was then removed under vacuum and the aqueous residue extracted with ether. The ether extracts were washed with water and then dried over magnesium sulfate. The ether solution was concentrated under reduced pressure and the residual oil placed on a column of dry silica gel; the product was eluted with hexane/ethyl acetate (1:1). Solvent was removed by evaporation in vacuo and the residue crystallized from 1-chlorobutane to afford 3.6 g (28%) of 4-(4-fluorophenyl)-5-(4-methylthiophenyl)-α,α-bis(trifluoromethyl)imidazole-2-methylamine, as colorless crystals, m.p. 150°-152°. IR: 3300 cm-1 (NH2). NMR: δ2.2 (s, 3H, CH3); 3.0 (s, 2H, NH2); 6.8-7.7 (m, 8H, aromatic).

Provenance & Evidence