2-甲基苯乙醛

反应条件: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: At 5° C., o-tolyl-acetaldehyde (3.50 g, 29 mmol) is added to a mixture of POCl3 (7.5 mL, 93 mmol) and DMF (8 mL). The mixture is stirred at 70° C. for 3 h before the reaction is quenched by adding water/ice and NaOAc (17 g) and extracted with EA (2×150 mL). The solvent of the organic extract is evaporated and the product is purified by CC on silica gel eluting with heptane:EA 9:1. The resulting oil (2.5 g) is dissolved in ethanol (5 mL) and then added dropwise to a freshly prepared solution of Na (318 mg, 13.8 mmol) and ethyl-2-mercaptoacetate (1.64 g, 13.6 mmol) in ethanol (15 mL). The reaction mixture is stirred at rt for 16 h, then at 70° C. for 2 h. 3 M aq. NaOH (15 mL) is added and the mixture is stirred at 70° C. for 2 h. The mixture is cooled to rt, diluted with water and extracted with DCM. The aqueous phase is acidified with aq. HCl and extracted with EA. The organic extract is dried over MgSO4 and the solvent is evaporated to give crude 4-o-tolyl-thiophene-2-carboxylic acid (790 mg) as a brown solid; LC-MS: tR=0.91 min. is quenched by adding water/ice and NaOAc (17 g) extracted with EA (2×150 mL) The solvent of the organic extract is evaporated the product is purified by CC on silica gel eluting with heptane:EA 9:1 The resulting oil (2.5 g) is dissolved in ethanol (5 mL) The reaction mixture is stirred at rt for 16 h at 70° C. for 2 h the mixture is stirred at 70° C. for 2 h The mixture is cooled to rt extracted with DCM extracted with EA The organic extract is dried over MgSO4 the solvent is evaporated

反应条件: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: At 5° C., o-tolyl-acetaldehyde (3.50 g, 29 mmol) is added to a mixture of POCl3 (7.5 mL, 93 mmol) and DMF (8 mL). The mixture is stirred at 70° C. for 3 h before the reaction is quenched by adding water/ice and NaOAc (17 g) and extracted with EA (2×150 mL). The solvent of the organic extract is evaporated and the product is purified by CC on silica gel eluting with heptane:EA 9:1. The resulting oil (2.5 g) is dissolved in ethanol (5 mL) and then added dropwise to a freshly prepared solution of Na (318 mg, 13.8 mmol) and ethyl-2-mercaptoacetate (1.64 g, 13.6 mmol) in ethanol (15 mL). The reaction mixture is stirred at rt for 16 h, then at 70° C. for 2 h. 3 M aq. NaOH (15 mL) is added and the mixture is stirred at 70° C. for 2 h. The mixture is cooled to rt, diluted with water and extracted with DCM. The aqueous phase is acidified with aq. HCl and extracted with EA. The organic extract is dried over MgSO4 and the solvent is evaporated to give crude 4-o-tolyl-thiophene-2-carboxylic acid (790 mg) as a brown solid; LC-MS: tR=0.91 min. is quenched by adding water/ice and NaOAc (17 g) extracted with EA (2×150 mL) The solvent of the organic extract is evaporated the product is purified by CC on silica gel eluting with heptane:EA 9:1 The resulting oil (2.5 g) is dissolved in ethanol (5 mL) The reaction mixture is stirred at rt for 16 h at 70° C. for 2 h the mixture is stirred at 70° C. for 2 h The mixture is cooled to rt extracted with DCM extracted with EA The organic extract is dried over MgSO4 the solvent is evaporated

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: The title compound was prepared from [2-amino-3-(trifluoromethyl)phenyl]-(3-hydroxy-phenyl)methanone and o-Tolyl-acetaldehyde following the procedure of Example 457: MS (ESI) m/z 380.126; HRMS: calcd for C23H16F3NO+H+, 380.12567; found (ESI, [M+H]+), 380.126.

反应条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a mixture of 2,2,2-trifluoroethylamine hydrochloride (0.271 g) in dichloromethane/water (15/0.5 mL) at 0° C. was added sodium nitrite (0.166 g) and the resulting yellow solution was stirred for 1 hour at 0° C. The reaction mixture was then cooled to −78° C. and 2-o-tolylacetaldehyde (0.134 g) was added, followed by zirconium(IV)tetrachloride. After stirring for 2 hrs at −78° C. cooling was stopped and methanol (3 mL) and saturated solution of NaHCO3 (10 mL) were added. The mixture was extracted with dichloromethane and the extracts were dried and concentrated. Evaporation residue (194 mg) was dissolved in methanol (3 ml) and solution was cooled to 0° C. Sodium borohydride (44 mg) was added and the reaction mixture was stirred for 25 minutes. K2CO3-solution (2M, 5 mL) was added to the reaction mixture, followed by water (5 mL) after 5 min and the resulting solution was extracted with EtOAc. Extracts were dried and concentrated and the residue was purified by separation method E (EtOAc/heptane). (Yield 121 mg). The reaction mixture was then cooled to −78° C. After stirring for 2 hrs at −78° C. cooling The mixture was extracted with dichloromethane the extracts were dried concentrated Evaporation residue (194 mg) was dissolved in methanol (3 ml) solution was cooled to 0° C Sodium borohydride (44 mg) was added the reaction mixture was stirred for 25 minutes K2CO3-solution (2M, 5 mL) was added to the reaction mixture followed by water (5 mL) after 5 min the resulting solution was extracted with EtOAc Extracts were dried concentrated the residue was purified by separation method E (EtOAc/heptane)

反应条件: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: At 5° C., o-tolyl-acetaldehyde (3.50 g, 29 mmol) is added to a mixture of POCl3 (7.5 mL, 93 mmol) and DMF (8 mL). The mixture is stirred at 70° C. for 3 h before the reaction is quenched by adding water/ice and NaOAc (17 g) and extracted with EA (2×150 mL). The solvent of the organic extract is evaporated and the product is purified by CC on silica gel eluting with heptane:EA 9:1. The resulting oil (2.5 g) is dissolved in ethanol (5 mL) and then added dropwise to a freshly prepared solution of Na (318 mg, 13.8 mmol) and ethyl-2-mercaptoacetate (1.64 g, 13.6 mmol) in ethanol (15 mL). The reaction mixture is stirred at rt for 16 h, then at 70° C. for 2 h. 3 M aq. NaOH (15 mL) is added and the mixture is stirred at 70° C. for 2 h. The mixture is cooled to rt, diluted with water and extracted with DCM. The aqueous phase is acidified with aq. HCl and extracted with EA. The organic extract is dried over MgSO4 and the solvent is evaporated to give crude 4-o-tolyl-thiophene-2-carboxylic acid (790 mg) as a brown solid; LC-MS: tR=0.91 min. is quenched by adding water/ice and NaOAc (17 g) extracted with EA (2×150 mL) The solvent of the organic extract is evaporated the product is purified by CC on silica gel eluting with heptane:EA 9:1 The resulting oil (2.5 g) is dissolved in ethanol (5 mL) The reaction mixture is stirred at rt for 16 h at 70° C. for 2 h the mixture is stirred at 70° C. for 2 h The mixture is cooled to rt extracted with DCM extracted with EA The organic extract is dried over MgSO4 the solvent is evaporated