1-bromo-4-(2,2,2-trifluoroethoxy)benzene

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

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

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

Conditions: temp:120.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a stirred solution of trifluoroethyl tosylate (1.5 g, 5.8 mmol) in DMF (20 mL) was added K2CO3 (4 g, 29.4 mmol) followed by addition of p-bromo phenol (1.1 g, 6.46 mmol) at RT under inert atmosphere. The reaction mixture was stirred at 120° C. for 6 h. The volatiles were evaporated under reduced pressure; the residue was diluted with water (5 mL) and extracted with ethyl acetate (3×30 mL). The organic layer was washed with water, brine and dried over anhydrous Na2SO4, filtered and concentrated in vacuo. The crude compound was purified by silica gel column chromatography eluting with 5% EtOAc/hexane to afford the desired product (0.8 g, 3.13 mmol, 53.3%) as semi solid. 1H NMR (200 MHz, CDCl3): δ 7.44-7.38 (m, 2H), 6.86-6.80 (m, 2H), 4.38-4.25 (m, 2H). The volatiles were evaporated under reduced pressure the residue was diluted with water (5 mL) extracted with ethyl acetate (3×30 mL) The organic layer was washed with water, brine dried over anhydrous Na2SO4 filtered concentrated in vacuo The crude compound was purified by silica gel column chromatography eluting with 5% EtOAc/hexane

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

Procedure: The title compound was prepared from rac-[(3,4-dichloro-phenyl)-(methoxy-methyl-carbamoyl)-methyl]-carbamic acid tert-butyl ester (Intermediate 9) and 1-bromo-4-(2,2,2-trifluoro-ethoxy)-benzene in analogy to Example 1a): MS (ISP): 478.1 and 480.1 (M+H)+, 378.2 and 380.0 ((M-Boc)+H)+ (100%).

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

Conditions: temp:120.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a stirred solution of trifluoroethyl tosylate (1.5 g, 5.8 mmol) in DMF (20 mL) was added K2CO3 (4 g, 29.4 mmol) followed by addition of p-bromo phenol (1.1 g, 6.46 mmol) at RT under inert atmosphere. The reaction mixture was stirred at 120° C. for 6 h. The volatiles were evaporated under reduced pressure; the residue was diluted with water (5 mL) and extracted with ethyl acetate (3×30 mL). The organic layer was washed with water, brine and dried over anhydrous Na2SO4, filtered and concentrated in vacuo. The crude compound was purified by silica gel column chromatography eluting with 5% EtOAc/hexane to afford the desired product (0.8 g, 3.13 mmol, 53.3%) as semi solid. 1H NMR (200 MHz, CDCl3): □ 7.44-7.38 (m, 2H), 6.86-6.80 (m, 2H), 4.38-4.25 (m, 2H). The volatiles were evaporated under reduced pressure the residue was diluted with water (5 mL) extracted with ethyl acetate (3×30 mL) The organic layer was washed with water, brine dried over anhydrous Na2SO4 filtered concentrated in vacuo The crude compound was purified by silica gel column chromatography eluting with 5% EtOAc/hexane

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Under an nitrogen atmosphere 1-benzyl-N,4-dimethyl-N-neopentyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-5-(trifluoromethyl)-1H-pyrrole-2-carboxamide (106 mg, 0.216 mmol) was dissolved in DMF (1 mL) and LiOH (4 mg, 0.216 mmol), bis(tri-tert-butylphosphine)palladium (0) (6 mg, 0.014 mmol) and 1-bromo-4-(2,2,2-trifluoroethoxy)benzene (50 mg, 0.196 mmol) were subsequently added. The reaction mixture was stirred at 80° C. under microwave irridation for 1 h. The mixture was cooled to RT and the reaction was stopped by addition of 1M NaOH solution (2 mL). The crude product was extracted with EtOAc (2×3 mL) and the combined organic layers were washed with water (3×1 mL), dried over Na2SO4, filtered and the solvent was removed under reduced pressure. The crude mass was purified by flash chromatography to give SC-260 (95 mg, 89.7%). The mixture was cooled to RT The crude product was extracted with EtOAc (2×3 mL) the combined organic layers were washed with water (3×1 mL) dried over Na2SO4 filtered the solvent was removed under reduced pressure The crude mass was purified by flash chromatography

Conditions: temp:120.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a stirred solution of trifluoroethyl tosylate (1.5 g, 5.8 mmol) in DMF (20 mL) was added K2CO3 (4 g, 29.4 mmol) followed by addition of p-bromo phenol (1.1 g, 6.46 mmol) at RT under inert atmosphere. The reaction mixture was stirred at 120° C. for 6 h. The volatiles were evaporated under reduced pressure; the residue was diluted with water (5 mL) and extracted with ethyl acetate (3×30 mL). The organic layer was washed with water, brine and dried over anhydrous Na2SO4, filtered and concentrated in vacuo. The crude compound was purified by silica gel column chromatography eluting with 5% EtOAc/hexane to afford the desired product (0.8 g, 3.13 mmol, 53.3%) as semi solid. 1H NMR (200 MHz, CDCl3): δ 7.44-7.38 (m, 2H), 6.86-6.80 (m, 2H), 4.38-4.25 (m, 2H). The volatiles were evaporated under reduced pressure the residue was diluted with water (5 mL) extracted with ethyl acetate (3×30 mL) The organic layer was washed with water, brine dried over anhydrous Na2SO4 filtered concentrated in vacuo The crude compound was purified by silica gel column chromatography eluting with 5% EtOAc/hexane

Conditions: temp:120.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a stirred solution of trifluoroethyl tosylate (1.5 g, 5.8 mmol) in DMF (20 mL) was added K2CO3 (4 g, 29.4 mmol) followed by addition of p-bromo phenol (1.1 g, 6.46 mmol) at RT under inert atmosphere. The reaction mixture was stirred at 120° C. for 6 h. The volatiles were evaporated under reduced pressure; the residue was diluted with water (5 mL) and extracted with ethyl acetate (3×30 mL). The organic layer was washed with water, brine and dried over anhydrous Na2SO4, filtered and concentrated in vacuo. The crude compound was purified by silica gel column chromatography eluting with 5% EtOAc/hexane to afford the desired product (0.8 g, 3.13 mmol, 53.3%) as semi solid. 1H NMR (200 MHz, CDCl3): δ 7.44-7.38 (m, 2H), 6.86-6.80 (m, 2H), 4.38-4.25 (m, 2H). The volatiles were evaporated under reduced pressure the residue was diluted with water (5 mL) extracted with ethyl acetate (3×30 mL) The organic layer was washed with water, brine dried over anhydrous Na2SO4 filtered concentrated in vacuo The crude compound was purified by silica gel column chromatography eluting with 5% EtOAc/hexane

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

Procedure: The title compound was prepared from rac-[(3,4-dichloro-phenyl)-(methoxy-methyl-carbamoyl)-methyl]-carbamic acid tert-butyl ester (Intermediate 9) and 1-bromo-4-(2,2,2-trifluoro-ethoxy)-benzene in analogy to Example 1a): MS (ISP): 478.1 and 480.1 (M+H)+, 378.2 and 380.0 ((M-Boc)+H)+ (100%).

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

Procedure: Following the method described in Example 89 for the synthesis of 2-bromo-4-chloro-1-(2,2,2-trifluoro-ethoxy)-benzene 4-bromo-phenol and trifluoro-methanesulfonic acid 2,2,2-trifluoro-ethyl ester gave 1-bromo-4-(2,2,2-trifluoro-ethoxy)-benzene (40% yield). 1H NMR (acetone-d6) δ 4.68 (q, 2H, J=8.5 Hz, CH2), 7.04 (d, 2H, J=9.1 Hz, Ar), 7.49 (d, 2H, J=9.1 Hz, Ar).