2-(3-chlorophenyl)acetaldehyde

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 2-(3-chlorophenyl)-acetaldehyde (5.80 g, 37.5 mmol) and phenylhydrazine (6.22 g, 57.5 mmol) in glacial acetic acid (150 mL) was saturated with nitrogen by bubbling N2 through the solution. The solution was then refluxed for about 2.5 hours. Solvent was removed in vacuo and the residue obtained was dissolved in DCM and washed with 1N HCl aqueous solution (2 times), saturated NaHCO3 aqueous solution (2 times) and brine (2 times), dried over anhydrous MgSO4, filtered and concentrated in vacuo. The crude product was purified by column chromatography on silica, eluting with EtOAc/hexane 1:6. The title compound was obtained as a reddish oil. Yield: 5.30 g, 62%. Rf=0.26 (silica, EtOAc/hexane 1:4). by bubbling N2 through the solution The solution was then refluxed for about 2.5 hours Solvent was removed in vacuo the residue obtained washed with 1N HCl aqueous solution (2 times), saturated NaHCO3 aqueous solution (2 times) and brine (2 times) dried over anhydrous MgSO4 filtered concentrated in vacuo The crude product was purified by column chromatography on silica eluting with EtOAc/hexane 1:6

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

Procedure: A solution of 2-(3-chlorophenyl)-acetaldehyde (5.80 g, 37.5 mmol) and phenylhydrazine (6.22 g, 57.5 mmol) in glacial acetic acid (150 mL) was saturated with nitrogen by bubbling N2 through the solution. The solution was then refluxed for about 2.5 hours. Solvent was removed in vacuo and the residue obtained was dissolved in DCM and washed with 1N HCl aqueous solution (2 times), saturated NaHCO3 aqueous solution (2 times) and brine (2 times), dried over anhydrous MgSO4, filtered and concentrated in vacuo. The crude product was purified by column chromatography on silica, eluting with EtOAc/hexane 1:6. The title compound was obtained as a reddish oil. Yield: 5.30 g, 62%. Rf=0.26 (silica, EtOAc/hexane 1:4). by bubbling N2 through the solution The solution was then refluxed for about 2.5 hours Solvent was removed in vacuo the residue obtained washed with 1N HCl aqueous solution (2 times), saturated NaHCO3 aqueous solution (2 times) and brine (2 times) dried over anhydrous MgSO4 filtered concentrated in vacuo The crude product was purified by column chromatography on silica eluting with EtOAc/hexane 1:6

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

Procedure: A suspension of LiAIH4 (1.90 g, 51 mmol) in anhydrous ether (250 mL) was stirred at room temperature tinder nitrogen for about 1 hour. The suspension was cooled to about 45° C. To it was added drops of a solution of 2-(3-chlorophenyl)-N-methoxy-N-methyl-acetamide (8.19 9, 38.3 mmol, see Preparation 1) in 10 mL of anhydrous tetrahydrofuran (THF). The mixture was warmed to about 0° C. and stirred for about 3 hours. The solution was then cooled to about 45° C. To this solution was slowly added a solution of KHSO4 (13 g) in water (about 30 mL) the resulting mixture was filtered through CELITE®. The filtrate was concentrated in vacuo, the resulting solution was diluted with DCM and washed with 1N HCl aqueous solution (2 times), and brine (2 times) dried over anhydrous MgSO4, filtered and concentrated in vacuo. The title compound was obtained as a liquid (5.80 g), which was used immediately in the next step without further purification. Rf=0.71 (silica, EtOAc/hexane 1:3). The suspension was cooled to about 45° C The mixture was warmed to about 0° C. stirred for about 3 hours The solution was then cooled to about 45° C was filtered through CELITE® The filtrate was concentrated in vacuo the resulting solution was diluted with DCM washed with 1N HCl aqueous solution (2 times), and brine (2 times) dried over anhydrous MgSO4 filtered concentrated in vacuo

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

Procedure: A solution of 2-(3-chlorophenyl)-acetaldehyde (5.80 g, 37.5 mmol) and phenylhydrazine (6.22 g, 57.5 mmol) in glacial acetic acid (150 mL) was saturated with nitrogen by bubbling N2 through the solution. The solution was then refluxed for about 2.5 hours. Solvent was removed in vacuo and the residue obtained was dissolved in DCM and washed with 1N HCl aqueous solution (2 times), saturated NaHCO3 aqueous solution (2 times) and brine (2 times), dried over anhydrous MgSO4, filtered and concentrated in vacuo. The crude product was purified by column chromatography on silica, eluting with EtOAc/hexane 1:6. The title compound was obtained as a reddish oil. Yield: 5.30 g, 62%. Rf=0.26 (silica, EtOAc/hexane 1:4). by bubbling N2 through the solution The solution was then refluxed for about 2.5 hours Solvent was removed in vacuo the residue obtained washed with 1N HCl aqueous solution (2 times), saturated NaHCO3 aqueous solution (2 times) and brine (2 times) dried over anhydrous MgSO4 filtered concentrated in vacuo The crude product was purified by column chromatography on silica eluting with EtOAc/hexane 1:6

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

Procedure: A suspension of LiAIH4 (1.90 g, 51 mmol) in anhydrous ether (250 mL) was stirred at room temperature tinder nitrogen for about 1 hour. The suspension was cooled to about 45° C. To it was added drops of a solution of 2-(3-chlorophenyl)-N-methoxy-N-methyl-acetamide (8.19 9, 38.3 mmol, see Preparation 1) in 10 mL of anhydrous tetrahydrofuran (THF). The mixture was warmed to about 0° C. and stirred for about 3 hours. The solution was then cooled to about 45° C. To this solution was slowly added a solution of KHSO4 (13 g) in water (about 30 mL) the resulting mixture was filtered through CELITE®. The filtrate was concentrated in vacuo, the resulting solution was diluted with DCM and washed with 1N HCl aqueous solution (2 times), and brine (2 times) dried over anhydrous MgSO4, filtered and concentrated in vacuo. The title compound was obtained as a liquid (5.80 g), which was used immediately in the next step without further purification. Rf=0.71 (silica, EtOAc/hexane 1:3). The suspension was cooled to about 45° C The mixture was warmed to about 0° C. stirred for about 3 hours The solution was then cooled to about 45° C was filtered through CELITE® The filtrate was concentrated in vacuo the resulting solution was diluted with DCM washed with 1N HCl aqueous solution (2 times), and brine (2 times) dried over anhydrous MgSO4 filtered concentrated in vacuo

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

Procedure: The title compound was prepared from [2-amino-3-(trifluoromethyl)phenyl]-(3-hydroxy-phenyl)methanone and (3-chloro-phenyl)-acetaldehyde following the procedure of Example 457: MS (ES) m/z 397.9; HRMS: calcd for C22H13ClF3NO+H+, 400.07105; found (ESI, [M+H]+), 400.0697.

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

Procedure: A solution of 2-(3-chlorophenyl)-acetaldehyde (5.80 g, 37.5 mmol) and phenylhydrazine (6.22 g, 57.5 mmol) in glacial acetic acid (150 mL) was saturated with nitrogen by bubbling N2 through the solution. The solution was then refluxed for about 2.5 hours. Solvent was removed in vacuo and the residue obtained was dissolved in DCM and washed with 1N HCl aqueous solution (2 times), saturated NaHCO3 aqueous solution (2 times) and brine (2 times), dried over anhydrous MgSO4, filtered and concentrated in vacuo. The crude product was purified by column chromatography on silica, eluting with EtOAc/hexane 1:6. The title compound was obtained as a reddish oil. Yield: 5.30 g, 62%. Rf=0.26 (silica, EtOAc/hexane 1:4) by bubbling N2 through the solution The solution was then refluxed for about 2.5 hours Solvent was removed in vacuo the residue obtained washed with 1N HCl aqueous solution (2 times), saturated NaHCO3 aqueous solution (2 times) and brine (2 times) dried over anhydrous MgSO4 filtered concentrated in vacuo The crude product was purified by column chromatography on silica eluting with EtOAc/hexane 1:6

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

Procedure: A suspension of LiAlH4 (1.90 g, 51 mmol) in anhydrous ether (250 mL) was stirred at room temperature under nitrogen for about 1 hour. The suspension was cooled to about −45° C. To it was added drops of a solution of 2-(3-chlorophenyl)-N-methoxy-N-methyl-acetamide (8.19 g, 38.3 mmol, see Preparation 1) in 10 mL of anhydrous tetrahydrofuran (THF). The mixture was warmed to about 0° C. and stirred for about 3 hours. The solution was then cooled to about −45° C. To this solution was slowly added a solution of KHSO4 (13 g) in water (about 30 mL) the resulting mixture was filtered through CELITE®. The filtrate was concentrated in vacuo, the resulting solution was diluted with DCM and washed with 1N HCl aqueous solution (2 times), and brine (2 times) dried over anhydrous MgSO4, filtered and concentrated in vacuo. The title compound was obtained as a liquid (5.80 g), which was used immediately in the next step without further purification. Rf=0.71 (silica, EtOAc/hexane 1:3). The suspension was cooled to about −45° C The mixture was warmed to about 0° C. stirred for about 3 hours The solution was then cooled to about −45° C was filtered through CELITE® The filtrate was concentrated in vacuo the resulting solution was diluted with DCM washed with 1N HCl aqueous solution (2 times), and brine (2 times) dried over anhydrous MgSO4 filtered concentrated in vacuo

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

Procedure: The mixture of Example 86A (5.73 g, 36.5 mmol) and Dess-Martin periodinane (18.6 g, 43.8 mmol) in 200 mL of dichloromethane was stirred under N2 atmosphere for 4 hours at room temperature. Then saturated NaHCO3 (500 mL) and Na2S2O3 (100 mL) was added with stirring for another 30 minutes. The mixture was extracted with dichloromethane (3×300 mL). The organic layers were combined, dried over Na2SO4, filtered, and concentrated. The crude product was purified by distillation under reduced pressure. The mixture was extracted with dichloromethane (3×300 mL) dried over Na2SO4 filtered concentrated The crude product was purified by distillation under reduced pressure

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

Procedure: Dess-Martin periodinane (1.02 g, 2.4 mmol) was diluted in anhydrous CH2Cl2 (25 mL) under argon, and when solution was affected, 3-chlorophenethyl alcohol (33, 0.313 g, 2.00 mmol) was added dropwise. The mixture was stirred for 2 h and 15 min at room temperature, and was then quenched by addition of 20 mL sat. aq. Na2S2O3. After stirring at room temperature for 15 min, the layers were separated, and the aqueous layer was extracted with CH2Cl2 (2×50 mL). The organic layer was washed with H2O and sat. aq. NaCl (50 mL each) and was dried over anhydrous sodium sulfate and concentrated. The resulting semisolid residue was triturated with 10% EtOAc in hexanes, and the solid was filtered out and discarded. The filtrate was concentrated, and the oily residue was purified by flash column chromatography (SiO2), eluting with a gradient of hexanes to 10% EtOAc in hexanes to afford the title compound as a clear yellow volatile oil (0.241 g, 78%). 1H-NMR (500 MHz; CDCl3): δ 9.75 (t, J=2.1 Hz, 1 H), 7.31-7.23 (m, 3 H), 7.11-7.09 (m, 1 H), 3.69 (d, J=2.1 Hz, 2 H). was then quenched by addition of 20 mL sat. aq. Na2S2O3 After stirring at room temperature for 15 min the layers were separated the aqueous layer was extracted with CH2Cl2 (2×50 mL) The organic layer was washed with H2O and sat. aq. NaCl (50 mL each) was dried over anhydrous sodium sulfate concentrated The resulting semisolid residue was triturated with 10% EtOAc in hexanes the solid was filtered out and The filtrate was concentrated the oily residue was purified by flash column chromatography (SiO2) eluting with a gradient of hexanes to 10% EtOAc in hexanes