methyl 3-(trifluoromethyl)-1H-pyrrole-2-carboxylate

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

Procedure: Into a 50-mL round-bottom flask purged and maintained with an inert atmosphere of nitrogen, was placed methyl 3-(trifluoromethyl)-1H-pyrrole-2-carboxylate and methyl 3-(perfluoroethyl)-1H-pyrrole-2-carboxylate (300 mg, 1.55 mmol, 1.00 equiv), (4-chlorophenyl)boronic acid (727 mg, 4.65 mmol, 3.00 equiv), Cu(AcO)2 (562 mg, 2.00 equiv), pyridine (491 mg, 6.21 mmol, 4.00 equiv) and dichloromethane (20 mL). The resulting solution was stirred for 2d at 20° C. The solids were filtered out. The resulting residue was applied onto a silica gel column with ethyl acetate/petroleum ether (1:15) to yield methyl 1-(4-chlorophenyl)-3-(trifluoromethyl)-1H-pyrrole-2-carboxylate and methyl 1-(4-chlorophenyl)-3-(perfluoroethyl)-1H-pyrrole-2-carboxylate as yellow oil. Into a 50-mL round-bottom flask purged maintained with an inert atmosphere of nitrogen The solids were filtered out

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Into a 100-mL round-bottom flask, was placed methyl 1-(benzenesulfonyl)-3-(trifluoromethyl)-1H-pyrrole-2-carboxylate and methyl 3-(perfluoroethyl)-1-(phenylsulfonyl)-1H-pyrrole-2-carboxylate (1.8 g, 5.40 mmol, 1.00 equiv) and tetrahydrofuran (15.0 mL). To the resulting mixture was then added NaOCH3 (1.17 g, 21.67 mmol, 4.01 equiv), in portions at 0° C. The resulting solution was stirred for 30 min at 0° C. in a water/ice bath. The reaction progress was monitored by LCMS. The reaction was then quenched by the addition of 2N hydrogen chloride until the solution became clear. The resulting solution was extracted with ethyl acetate (3×20 mL) and the organic layers combined. The resulting mixture was washed with sodium chloride (1×20 mL). The resulting mixture was dried over anhydrous sodium sulfate and concentrated under vacuum to yield methyl 3-(trifluoromethyl)-1H-pyrrole-2-carboxylate and methyl 3-(perfluoroethyl)-1-(phenylsulfonyl)-1H-pyrrole-2-carboxylate as a yellow solid. The yellow soli, was used in the next step without further purification. Into a 100-mL round-bottom flask, was placed at 0° C The reaction was then quenched by the addition of 2N hydrogen chloride until the solution The resulting solution was extracted with ethyl acetate (3×20 mL) The resulting mixture was washed with sodium chloride (1×20 mL) The resulting mixture was dried over anhydrous sodium sulfate concentrated under vacuum

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

Procedure: Into a 100-mL round-bottom flask purged and maintained with an inert atmosphere of nitrogen, was placed methyl 3-(trifluoromethyl)-1H-pyrrole-2-carboxylate (810 mg, 4.19 mmol, 1.00 equiv), phenylboronic acid (1.54 g, 12.63 mmol, 3.01 equiv), Cu(OAc)2 (1.52 g, 8.37 mmol, 2.00 equiv), pyridine (1.327 g, 16.78 mmol, 4.00 equiv), 4 {acute over (Å)} Molecular Sieves (1.2 g) and dichloromethane (20.0 mL). The resulting solution was stirred for 2 days at 20° C. The reaction progress was monitored by LCMS. The solids were filtered out and the resulting mixture was concentrated under vacuum. The resulting residue was applied onto a silica gel column with ethyl acetate/petroleum ether (1:9) to yield methyl 1-phenyl-3-(trifluoromethyl)-1H-pyrrole-2-carboxylate as a pink solid (0.67 g, 59%) Into a 100-mL round-bottom flask purged maintained with an inert atmosphere of nitrogen The solids were filtered out the resulting mixture was concentrated under vacuum

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

Procedure: The title compound was prepared by (a) reacting the product prepared in Step B of Example 1 and 4-methoxyphenylboronic acid according to the procedure described in Example 1, Step C, (b) then reacting the resulting product according to the procedure in Example 1, Step D, (c) then reacting the resulting product with ethyl 3-(2,3-difluoro-4-hydroxyphenyl)propanoate according to the procedure described in Example 1, Step E, and Example 2.

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

Procedure: The title compound was prepared by (a) reacting the product prepared in Step B of Example 1 and 4-methoxyphenylboronic acid according to the procedure described in Example 1, Step C, (b) then reacting the resulting product according to the procedure in Example 1, Step D, and (c) then reacting the resulting product with ethyl 3-(2,3-difluoro-4-hydroxyphenyl)propanoate according to the procedure described in Example 1, Steps E and F.

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

Procedure: The title compound was prepared by (a) reacting the product prepared in Step B of Example 1 and 4-methoxyphenylboronic acid according to the procedure described in Example 1, Step C, (b) then reacting the resulting product according to the procedure in Example 1, Step D, (c) then reacting the resulting product with ethyl 3-(2,3-dimethyl-4-hydroxyphenyl)propanoate according to the procedure in Example 1, Step E, and Example 2.

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

Procedure: The title compound was prepared by (a) reacting the product prepared in Step B of Example 1 and 4-methoxyphenylboronic acid according to the procedure described in Example 1, Step C, (b) then reacting the resulting product according to the procedure in Example 1, Step D, and (c) then reacting the resulting product with ethyl 3-(2,3-dimethyl-4-hydroxyphenyl)propanoate according to the procedures described in Example 1, Steps E and F.

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

Procedure: The title compound was prepared by (a) reacting the product prepared in Step B of Example 1 and 4-bromophenylboronic acid according to the procedure described in Example 1, Step C, (b) then reacting the resulting product according to the procedure in Example 1, Step D, and (c) then reacting the resulting product with ethyl 3-(2,3-dimethyl-4-hydroxyphenyl)propanoate according to the procedures described in Example 1, Steps E and F.

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

Procedure: The title compound was prepared by (a) reacting the product prepared in Step B of Example 1 and 4-bromophenylboronic acid according to the procedure described in Example 1, Step C, (b) then reacting the resulting product according to the procedure in Example 1, Step D, (c) then reacting the resulting product with ethyl 3-(2,3-difluoro-4-hydroxyphenyl)propanoate according to the procedure described in Example 1, Step E, and Example 2.

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

Procedure: The title compound was prepared by (a) reacting the product prepared in Step B of Example 1 and 4-bromophenylboronic acid according to the procedure described in Example 1, Step C, (b) then reacting the resulting product according to the procedure in Example 1, Step D, and (c) then reacting the resulting product with ethyl 3-(2,3-difluoro-4-hydroxyphenyl)propanoate according to the procedure described in Example 1, Steps E and F.

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

Procedure: The title compound was prepared by (a) reacting the product prepared in Step B of Example 1 and phenylboronic acid according to the procedure described in Example 1, Step C, (b) then reacting the resulting product according to the procedure in Example 1, Step D, (c) then reacting the resulting product with ethyl 3-(2,3-dimethyl-4-hydroxyphenyl)propanoate according to the procedure in Example 1, Step E, and Example 2.

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

Procedure: The title compound was prepared by (a) reacting the product prepared in Step B of Example 1 and 4-bromophenylboronic acid according to the procedure described in Example 1, Step C, (b) then reacting the resulting product according to the procedure in Example 1, Step D, (c) then reacting the resulting product with ethyl 3-(2,3-dimethyl-4-hydroxyphenyl)propanoate according to the procedure in Example 1, Step E, and Example 2.