2-(2-methoxyphenyl)acetaldehyde

Conditions: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of n-butyl lithium (2.5 M, 250 mL, 0.62 mol) was added to a solution of N-Boc-2-aminothiazole (56 g, 0.28 mol) in anhydrous tetrahydrofuran (500 mL) was added at −78° C. After the addition was completed, the mixture was allowed to stir at −78° C. for one hour. A solution of (2-methoxy-phenyl)-acetaldehyde (36 g, 0.24 mol) in tetrahydrofuran (100 mL) was slowly added to the reaction mixture while maintaining a temperature of −78° C. The mixture was allowed to warm to room temperature and stirred for 15 hours. The reaction was quenched with a saturated aqueous solution of ammonium chloride (1000 mL) and extracted three times with ethyl acetate (400 mL). The combined organic layers were washed with a saturated aqueous solution of sodium chloride, dried over sodium sulfate, and evaporated to dryness. The crude product was purified by column chromatography to give the pure product (28 g, 0.080 mol, 28%). was added at −78° C After the addition while maintaining a temperature of −78° C to warm to room temperature stirred for 15 hours The reaction was quenched with a saturated aqueous solution of ammonium chloride (1000 mL) extracted three times with ethyl acetate (400 mL) The combined organic layers were washed with a saturated aqueous solution of sodium chloride dried over sodium sulfate evaporated to dryness The crude product was purified by column chromatography

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

Procedure: A solution of pyridine complex with sulfur trioxide (134 g, 0.842 mol) in dimethylsulfoxide (150 mL) was slowly added to a solution of 2-(2-methoxy-phenyl)-ethanol (43 g, 0.28 mol) and triethylamine (86 g, 0.85 mol) in dichloromethane (500 mL) at 0° C. After being stirred 30 min, the mixture was poured into a saturated aqueous solution of sodium chloride and the organic layer was washed with dilute hydrochloric acid, a saturated aqueous solution of sodium chloride, dried over sodium sulfate and evaporated to dryness to give (2-methoxy-phenyl)-acetaldehyde (36 g, 0.24 mol, 86%) which was used in the next step directly. the organic layer was washed with dilute hydrochloric acid a saturated aqueous solution of sodium chloride, dried over sodium sulfate evaporated to dryness

Conditions: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of n-butyl lithium (2.5 M, 250 mL, 0.62 mol) was added to a solution of N-Boc-2-aminothiazole (56 g, 0.28 mol) in anhydrous tetrahydrofuran (500 mL) was added at −78° C. After the addition was completed, the mixture was allowed to stir at −78° C. for one hour. A solution of (2-methoxy-phenyl)-acetaldehyde (36 g, 0.24 mol) in tetrahydrofuran (100 mL) was slowly added to the reaction mixture while maintaining a temperature of −78° C. The mixture was allowed to warm to room temperature and stirred for 15 hours. The reaction was quenched with a saturated aqueous solution of ammonium chloride (1000 mL) and extracted three times with ethyl acetate (400 mL). The combined organic layers were washed with a saturated aqueous solution of sodium chloride, dried over sodium sulfate, and evaporated to dryness. The crude product was purified by column chromatography to give the pure product (28 g, 0.080 mol, 28%). was added at −78° C After the addition while maintaining a temperature of −78° C to warm to room temperature stirred for 15 hours The reaction was quenched with a saturated aqueous solution of ammonium chloride (1000 mL) extracted three times with ethyl acetate (400 mL) The combined organic layers were washed with a saturated aqueous solution of sodium chloride dried over sodium sulfate evaporated to dryness The crude product was purified by column chromatography

Conditions: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of n-butyl lithium (2.5 M, 250 mL, 0.62 mol) was added to a solution of N-Boc-2-aminothiazole (56 g, 0.28 mol) in anhydrous tetrahydrofuran (500 mL) was added at −78° C. After the addition was completed, the mixture was allowed to stir at −78° C. for one hour. A solution of (2-methoxy-phenyl)-acetaldehyde (36 g, 0.24 mol) in tetrahydrofuran (100 mL) was slowly added to the reaction mixture while maintaining a temperature of −78° C. The mixture was allowed to warm to room temperature and stirred for 15 hours. The reaction was quenched with a saturated aqueous solution of ammonium chloride (1000 mL) and extracted three times with ethyl acetate (400 mL). The combined organic layers were washed with a saturated aqueous solution of sodium chloride, dried over sodium sulfate, and evaporated to dryness. The crude product was purified by column chromatography to give the pure product (28 g, 0.080 mol, 28%). was added at −78° C After the addition while maintaining a temperature of −78° C to warm to room temperature stirred for 15 hours The reaction was quenched with a saturated aqueous solution of ammonium chloride (1000 mL) extracted three times with ethyl acetate (400 mL) The combined organic layers were washed with a saturated aqueous solution of sodium chloride dried over sodium sulfate evaporated to dryness The crude product was purified by column chromatography

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

Procedure: A solution of pyridine complex with sulfur trioxide (134 g, 0.842 mol) in dimethylsulfoxide (150 mL) was slowly added to a solution of 2-(2-methoxy-phenyl)-ethanol (43 g, 0.28 mol) and triethylamine (86 g, 0.85 mol) in dichloromethane (500 mL) at 0° C. After being stirred 30 min, the mixture was poured into a saturated aqueous solution of sodium chloride and the organic layer was washed with dilute hydrochloric acid, a saturated aqueous solution of sodium chloride, dried over sodium sulfate and evaporated to dryness to give (2-methoxy-phenyl)-acetaldehyde (36 g, 0.24 mol, 86%) which was used in the next step directly. the organic layer was washed with dilute hydrochloric acid a saturated aqueous solution of sodium chloride, dried over sodium sulfate evaporated to dryness

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

Procedure: (2-Methoxyphenyl)acetaldehyde is prepared by oxidation of 2-(2-methoxyphenyl)ethanol according to the procedure disclosed in J. Org. Chem., 49:1720, 1999. A mixture of (2-methoxyphenyl)acetaldehyde (3.8 g, 25.3 mmol) and dimethylformamide dimethyl acetal (4.52 g, 37.9 mmol) is stirred at room temperature for 1 hour. Excess of the acetal is removed under reduced pressure to leave 4.68 g of 3-dimethylamino-2-(2-methoxyphenyl)propenal (90%). Excess of the acetal is removed under reduced pressure

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 (2-Methoxy-phenyl)-acetaldehyde following the procedure of Example 457: MS (ESI) m/z 396; HRMS: calcd for C23H16F3NO2+H+, 396.12059; found (ESI, [M+H]+), 396.1223.

Conditions: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of n-butyl lithium (2.5 M, 250 mL, 0.62 mol) was added to a solution of N-Boc-2-aminothiazole (56 g, 0.28 mol) in anhydrous tetrahydrofuran (500 mL) was added at −78° C. After the addition was completed, the mixture was allowed to stir at −78° C. for one hour. A solution of (2-methoxy-phenyl)-acetaldehyde (36 g, 0.24 mol) in tetrahydrofuran (100 mL) was slowly added to the reaction mixture while maintaining a temperature of −78° C. The mixture was allowed to warm to room temperature and stirred for 15 hours. The reaction was quenched with a saturated aqueous solution of ammonium chloride (1000 mL) and extracted three times with ethyl acetate (400 mL). The combined organic layers were washed with a saturated aqueous solution of sodium chloride, dried over sodium sulfate, and evaporated to dryness. The crude product was purified by column chromatography to give the pure product (28 g, 0.080 mol, 28%). was added at −78° C After the addition while maintaining a temperature of −78° C to warm to room temperature stirred for 15 hours The reaction was quenched with a saturated aqueous solution of ammonium chloride (1000 mL) extracted three times with ethyl acetate (400 mL) The combined organic layers were washed with a saturated aqueous solution of sodium chloride dried over sodium sulfate evaporated to dryness The crude product was purified by column chromatography

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

Procedure: A solution of pyridine complex with sulfur trioxide (134 g, 0.842 mol) in dimethylsulfoxide (150 mL) was slowly added to a solution of 2-(2-methoxy-phenyl)-ethanol (43 g, 0.28 mol) and triethylamine (86 g, 0.85 mol) in dichloromethane (500 mL) at 0° C. After being stirred 30 min, the mixture was poured into a saturated aqueous solution of sodium chloride and the organic layer was washed with dilute hydrochloric acid, a saturated aqueous solution of sodium chloride, dried over sodium sulfate and evaporated to dryness to give (2-methoxy-phenyl)-acetaldehyde (36 g, 0.24 mol, 86%) which was used in the next step directly. the organic layer was washed with dilute hydrochloric acid a saturated aqueous solution of sodium chloride, dried over sodium sulfate evaporated to dryness