ethyl 4-(trifluoromethyl)-1H-pyrrole-3-carboxylate

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of potassium t-butoxide (4.5 g, 0.04 mol) in tetrahydrofuran is treated dropwise with a solution of ethyl 4-(trifluoromethyl)pyrrole-3-carboxylate (8.3 g, 0.04 mol) in tetrahydrofuran over a 20 minute period at 20°-25° C., stirred for 30 minutes, treated dropwise with methyl iodide (5.7 g, 0.04 mol), stirred at room temperature for 24 hours and poured into water. The resultant mixture is extracted with ether and the combined extracts are washed with brine, dried (MgSO4) and concentrated in vacuo to afford a brown oil residue. The residue is distilled using a Kugelrohr distillation apparatus to give a gummy solid at 80°-85° C./0.2 mm Hg. The solid is purified using ether and basic alumina to yield the title compound as a clear oil, 6.37 g (72%), identified by NMR and elemental analyses. stirred at room temperature for 24 hours The resultant mixture is extracted with ether the combined extracts are washed with brine dried (MgSO4) concentrated in vacuo to afford a brown oil residue The residue is distilled a Kugelrohr distillation apparatus to give a gummy solid at 80°-85° C./0.2 mm Hg The solid is purified

Conditions: temp:-60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of potassium t-butoxide (8.11 g, 0.075 mol) in tetrahydrofuran at -60° C. is treated dropwise with a mixture of ethyl 4,4,4-trifluorocrotonate (10.5 g, 0.063 mol) and p-tolylsulfonylmethylisocyanide (12.2 g, 0.063 mol) in tetrahydrofuran over a 1 hour period, stirred at -60° C. for 30 minutes, allowed to warm to room temperature and quenched with water. The reaction mixture is extracted with ether and ethyl acetate. The combined extracts are washed with brine, dried (MgSO4) and concentrated in vacuo to give a solid residue. Recrystallization from 1,2-dichloroethane affords the title compound as a tan solid, 7.3 g (56%), mp 163°-164° C. to warm to room temperature quenched with water The reaction mixture is extracted with ether and ethyl acetate The combined extracts are washed with brine dried (MgSO4) concentrated in vacuo to give a solid residue Recrystallization from 1,2-dichloroethane

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:20.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 1 g of ethyl 3-trifluoromethyl-1H-pyrrole-4-carboxylate of Step A was introduced into 10 ml of tetrahydrofuran, followed, at 0° C. by 240 mg of sodium hydride at 50% in vaseline oil in small portions. After stirring for 30 minutes at 20° C. and cooling to 0° C., a solution of 0.45 ml of propargyl bromide in 1 ml of tetrahydrofuran was added with stirring for 30 minutes at 0° C., then for 1 hour at 20° C., followed by cooling again to 0° C. A little sodium hydride was added then 0.45 ml of propargyl bromide in solution in 1 ml of tetrahydrofuran with stirring at 0° C. The mixture was poured into water and extracted with methylene chloride. The extracts were concentrated to dryness by distilling under reduced pressure and the residue was chromatographed over silica. Elution with a mixture of hexane and ethyl acetate (8-2) yielded 0.950 g of ethyl 1-(2-propynyl)-3-trifluoromethyl-1H-pyrrole-4-carboxylate melting at 58° C. cooling to 0° C. with stirring for 30 minutes at 0° C. for 1 hour at 20° C. by cooling again to 0° C extracted with methylene chloride The extracts were concentrated to dryness by distilling under reduced pressure the residue was chromatographed over silica Elution with a mixture of hexane and ethyl acetate (8-2)

Conditions: temp:20.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 7.4 g of ethyl 4,4,4-trifluoro-(E)-butenoate (E. T. McBee, J. Am. Soc. Vol. 76 p. 3724 (1924)) and 8.6 g of tosylmethyl isocyanide were introduced into 200 ml of a mixture of dimethylsulfoxide and ethyl ether (1-2) and then 2.9 g of sodium hydride at 50% in vaseline were added in small portions. Hydrogen evolved and after stirring for 30 minutes at 20° C., a few drops of acetic acid were added. The mixture was poured into a mixture of water and ice and was extracted with ether. The extracts were concentrated to dryness by distilling under reduced pressure and the residue was chromatographed over silica. Eluting with a mixture of hexane and ethyl acetate (7-3) to yielded 6.6 g of ethyl 3-trifluoromethyl-1H-pyrrol-4-carboxylate melting at 165° C. was extracted with ether The extracts were concentrated to dryness by distilling under reduced pressure the residue was chromatographed over silica Eluting with a mixture of hexane and ethyl acetate (7-3)

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of potassium t-butoxide (4.5 g, 0.04 mol) in tetrahydrofuran is treated dropwise with a solution of ethyl 4-(trifluoromethyl)pyrrole-3-carboxylate (8.3 g, 0.04 mol) in tetrahydrofuran over a 20 minute period at 20°-25° C., stirred for 30 minutes, treated dropwise with methyl iodide (5.7 g, 0.04 mol), stirred at room temperature for 24 hours and poured into water. The resultant mixture is extracted with ether and the combined extracts are washed with brine, dried (MgSO4) and concentrated in vacuo to afford a brown oil residue. The residue is distilled using a Kugelrohr distillation apparatus to give a gummy solid at 80°-85° C./0.2 mm Hg. The solid is purified using ether and basic alumina to yield the title compound as a clear oil, 6.37 g (72%), identified by NMR and elemental analyses. stirred at room temperature for 24 hours The resultant mixture is extracted with ether the combined extracts are washed with brine dried (MgSO4) concentrated in vacuo to afford a brown oil residue The residue is distilled a Kugelrohr distillation apparatus to give a gummy solid at 80°-85° C./0.2 mm Hg The solid is purified

Conditions: temp:-60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of potassium t-butoxide (8.11 g, 0.075 mol) in tetrahydrofuran at -60° C. is treated dropwise with a mixture of ethyl 4,4,4-trifluorocrotonate (10.5 g, 0.063 mol) and p-tolylsulfonylmethylisocyanide (12.2 g, 0.063 mol) in tetrahydrofuran over a 1 hour period, stirred at -60° C. for 30 minutes, allowed to warm to room temperature and quenched with water. The reaction mixture is extracted with ether and ethyl acetate. The combined extracts are washed with brine, dried (MgSO4) and concentrated in vacuo to give a solid residue. Recrystallization from 1,2-dichloroethane affords the title compound as a tan solid, 7.3 g (56%), mp 163°-164° C. to warm to room temperature quenched with water The reaction mixture is extracted with ether and ethyl acetate The combined extracts are washed with brine dried (MgSO4) concentrated in vacuo to give a solid residue Recrystallization from 1,2-dichloroethane

Conditions: temp:-60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of potassium t-butoxide (8.11 g, 0.075 mol) in tetrahydrofuran at -60° C. is treated dropwise with a mixture of ethyl 4,4,4-trifluorocrotonate (10.5 g, 0.063 mol) and p-tolylsulfonylmethylisocyanide (12.2 g, 0.063 mol) in tetrahydrofuran over a 1 hour period, stirred at -60° C. for 30 minutes, allowed to warm to room temperature and quenched with water. The reaction mixture is extracted with ether and ethyl acetate. The combined extracts are washed with brine, dried (MgSO4) and concentrated in vacuo to give a solid residue. Recrystallization from 1,2-dichloroethane affords the title compound as a tan solid, 7.3 g (56%), mp 163°-164° C. to warm to room temperature quenched with water The reaction mixture is extracted with ether and ethyl acetate The combined extracts are washed with brine dried (MgSO4) concentrated in vacuo to give a solid residue Recrystallization from 1,2-dichloroethane

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:20.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 7.4 g of ethyl 4,4,4-trifluoro-(E)-butenoate (E. T. McBee, J. Am. Soc. Vol. 76 p. 3724 (1924)) and 8.6 g of tosylmethyl isocyanide were introduced into 200 ml of a mixture of dimethylsulfoxide and ethyl ether (1-2) and then 2.9 g of sodium hydride at 50% in vaseline were added in small portions. Hydrogen evolved and after stirring for 30 minutes at 20° C., a few drops of acetic acid were added. The mixture was poured into a mixture of water and ice and was extracted with ether. The extracts were concentrated to dryness by distilling under reduced pressure and the residue was chromatographed over silica. Elution with a mixture of hexane and ethyl acetate (7-3) to yielded 6.6 g of ethyl 3-trifluoromethyl-1H-pyrrol-4-carboxylate melting at 165° C. was extracted with ether The extracts were concentrated to dryness by distilling under reduced pressure the residue was chromatographed over silica Elution with a mixture of hexane and ethyl acetate (7-3)