4-Chloro-2-(trifluoromethyl)benzaldehyde

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

Conditions: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Add 4-chloro-2-trifluoromethyl-benzonitrile to formic acid (96%) (15 mL) and water (3 mL). Add nickel-aluminum alloy (1260 mg). Heat at 100° C. overnight. Dilute with ethyl acetate and filter through Celite®. Extract the filtrate with 1 N sodium hydroxide and saturated aqueous sodium chloride, dry (sodium sulfate), filter, and concentrate to give 4-chloro-2-trifluoromethylbenzaldehyde (555 mg, 87%): 1H NMR (400 MHz, MeOH-d4) δ 10.29 (m, 1H), 8.10 (d, 1H, J=8.4 Hz), 7.91 (d, 1H, J=1.6 Hz), 7.85 (dd, 1H, J=8.4, 1.6 Hz). filter through Celite® Extract the filtrate with 1 N sodium hydroxide and saturated aqueous sodium chloride dry (sodium sulfate) filter concentrate

Conditions: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Add 4-chloro-2-trifluoromethyl-benzonitrile to formic acid (96%) (15 mL) and water (3 mL). Add nickel-aluminum alloy (1260 mg). Heat at 100° C. overnight. Dilute with ethyl acetate and filter through Celite®. Extract the filtrate with 1 N sodium hydroxide and saturated aqueous sodium chloride, dry (sodium sulfate), filter, and concentrate to give 4-chloro-2-trifluoromethylbenzaldehyde (555 mg, 87%): 1H NMR (400 MHz, MeOH-d4) δ 10.29 (m, 1H), 8.10 (d, 1H, J=8.4 Hz), 7.91 (d, 1H, J=1.6 Hz), 7.85 (dd, 1H, J=8.4, 1.6 Hz). filter through Celite® Extract the filtrate with 1 N sodium hydroxide and saturated aqueous sodium chloride dry (sodium sulfate) filter concentrate

Conditions: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Add 4-chloro-2-trifluoromethyl-benzonitrile to formic acid (96%) (15 mL) and water (3 mL). Add nickel-aluminum alloy (1260 mg). Heat at 100° C. overnight. Dilute with ethyl acetate and filter through Celite®. Extract the filtrate with 1 N sodium hydroxide and saturated aqueous sodium chloride, dry (sodium sulfate), filter, and concentrate to give 4-chloro-2-trifluoromethylbenzaldehyde (555 mg, 87%): 1H NMR (400 MHz, MeOH-d4) δ 10.29 (m, 1H), 8.10 (d, 1H, J=8.4 Hz), 7.91 (d, 1H, J=1.6 Hz), 7.85 (dd, 1H, J=8.4, 1.6 Hz). filter through Celite® Extract the filtrate with 1 N sodium hydroxide and saturated aqueous sodium chloride dry (sodium sulfate) filter concentrate

Conditions: temp:22.01; 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: To a stirred solution of 4-chloro-2-(trifluoromethyl)benzaldehyde (17; 4.20 g, 20.0 mmol) in methanol (25 mL) was added triethoxymethane (3.60 g, 24.0 mmol) at 0° C. The resulting reaction mixture was warmed to room temperature and stirred for 12 h. A solution of MeONa in methanol was added to adjust the pH=10. The solvent was removed under reduced pressure and the resulting residue was diluted with water. The mixture was extracted with ethyl acetate (3×50 mL) and the combined organic layers were dried (Na2SO4) and concentrated under reduced pressure to give 4-chloro-1-(dimethoxymethyl)-2-(trifluoromethyl)benzene 18 (3.20 g, 12.6 mmol, 63%). The resulting reaction mixture The solvent was removed under reduced pressure the resulting residue was diluted with water The mixture was extracted with ethyl acetate (3×50 mL) the combined organic layers were dried (Na2SO4) concentrated under reduced pressure

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

Procedure: To a solution of (5Z)-4-[(2-hydroxy-2-methylpropyl)amino]-5-(piperidin-4-ylmethylidene)-1,3-thiazol-2(5H)-one dihydrochloride (200 mg) in DMF (2 mL) was added a solution of triethylamine (0.32 mL) and 4-chloro-2-(trifluoromethyl)benzaldehyde (117 mg) in DMF (1 mL). The reaction mixture was stirred at room temperature for 1 hr, and sodium triacetoxyborohydride (501 mg) was added. The reaction mixture was stirred at room temperature overnight, saturated aqueous sodium hydrogen carbonate solution was added, and the mixture was extracted with ethyl acetate. The extract was washed with water and saturated brine, and dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate/hexane) and recrystallized from ethyl acetate/heptane to give the title compound (82 mg). The reaction mixture was stirred at room temperature overnight the mixture was extracted with ethyl acetate The extract was washed with water and saturated brine dried over anhydrous magnesium sulfate the solvent was evaporated under reduced pressure The residue was purified by silica gel column chromatography (ethyl acetate/hexane) recrystallized from ethyl acetate/heptane

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

Procedure: To a solution of (5Z)-5-(piperidin-4-ylmethylidene)-4-(prop-2-yn-1-ylamino)-1,3-thiazol-2(5H)-one dihydrochloride (1.00 g) in DMF (15.5 mL) were added 4-chloro-2-(trifluoromethyl)benzaldehyde (1.10 g) and triethylamine (1.95 mL). The reaction mixture was stirred at room temperature for 1.5 hr, and sodium triacetoxyborohydride (2.28 g) was added. The reaction mixture was stirred at room temperature for 1 hr, poured into water, and the mixture was extracted with ethyl acetate. The extract was washed with saturated brine, and dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate/hexane) to give the title compound (1.04 g). The reaction mixture was stirred at room temperature for 1 hr the mixture was extracted with ethyl acetate The extract was washed with saturated brine dried over anhydrous magnesium sulfate the solvent was evaporated under reduced pressure The residue was purified by silica gel column chromatography (ethyl acetate/hexane)

Conditions: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Add 4-chloro-2-trifluoromethyl-benzonitrile to formic acid (96%) (15 mL) and water (3 mL). Add nickel-aluminum alloy (1260 mg). Heat at 100° C. overnight. Dilute with ethyl acetate and filter through Celite®. Extract the filtrate with 1 N sodium hydroxide and saturated aqueous sodium chloride, dry (sodium sulfate), filter, and concentrate to give 4-chloro-2-trifluoromethylbenzaldehyde (555 mg, 87%): 1H NMR (400 MHz, MeOH-d4) δ 10.29 (m, 1H), 8.10 (d, 1H, J=8.4 Hz), 7.91 (d, 1H, J=1.6 Hz), 7.85 (dd, 1H, J=8.4, 1.6 Hz). filter through Celite® Extract the filtrate with 1 N sodium hydroxide and saturated aqueous sodium chloride dry (sodium sulfate) filter concentrate

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