2-chloro-3-fluorobenzaldehyde

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 2-Chloro-3-fluorobenzaldehyde (2.5 g) and (R)-(+)-2-methyl-2-propanesulfinamide were dissolved in dichloromethane (50 ml), and then titanium(IV) isopropoxide (23.6 ml) was added. The mixture was heated for three hours under reflux, then poured onto ice (150 g) and stirred vigorously for ten minutes. The mixture was filtered through kieselguhr and the filtrate was extracted with dichloromethane (3×50 ml). The organic phase was dried (Na2SO4), filtered and concentrated under reduced pressure. The product (4 g) was used further without further purification. The mixture was heated for three hours under reflux poured onto ice (150 g) The mixture was filtered through kieselguhr the filtrate was extracted with dichloromethane (3×50 ml) The organic phase was dried (Na2SO4) filtered concentrated under reduced pressure The product (4 g) was used further without further purification

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Compound C-1 was prepared in analogy to compound C by using ethyl acetoacetate and 2-chloro-3-fluorobenzaldehyde instead of methyl acetoacetate and 2-chloro-4-fluorobenzaldehyde.

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Compound C-1 was prepared in analogy to compound C by using ethyl acetoacetate and 2-chloro-3-fluorobenzaldehyde instead of methyl acetoacetate and 2-chloro-4-fluorobenzaldehyde.

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of 460 mg of 2-chloro-3-fluorobenzaldehyde, 360 mg of methyl 3-aminocrotonate and 820 mg of 2-(N-benzyl-N-methylamino)ethyl 3-aminocrotonate in 4 ml of 2-propanol was refluxed for 8 hours, and then the solvent was distilled off under reduced pressure. The residue was purified by a column chromatography on silica gel to provide 860 mg of the desired compound (110). was refluxed for 8 hours the solvent was distilled off under reduced pressure The residue was purified by a column chromatography on silica gel

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 2-Chloro-3-fluorobenzaldehyde (2.5 g) and (R)-(+)-2-methyl-2-propanesulfinamide were dissolved in dichloromethane (50 ml), and then titanium(IV) isopropoxide (23.6 ml) was added. The mixture was heated for three hours under reflux, then poured onto ice (150 g) and stirred vigorously for ten minutes. The mixture was filtered through kieselguhr and the filtrate was extracted with dichloromethane (3×50 ml). The organic phase was dried (Na2SO4), filtered and concentrated under reduced pressure. The product (4 g) was used further without further purification. The mixture was heated for three hours under reflux poured onto ice (150 g) The mixture was filtered through kieselguhr the filtrate was extracted with dichloromethane (3×50 ml) The organic phase was dried (Na2SO4) filtered concentrated under reduced pressure The product (4 g) was used further without further purification

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: The title compound was prepared in analogy to Example 2 with Procedure B shown in Scheme 5 by using 2-chloro-3-fluoro-benzaldehyde, ethyl acetoacetate, 1-methyl-1H-imidazole-2-carbonitrile and (S)-morpholine-3-carboxylic acid instead of 2-chloro-4-fluoro-benzaldehyde, methyl acetoacetate, thiazole-2-carbonitrile and (S)-4,4-difluoro-pyrrolidine-2-carboxylic acid. The stereochemistry of Example 97 was determined by comparing its 1H NMR data and HPLC retention time with Example 2.

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: The title compound was prepared in analogy to Example 2 with Procedure B shown in Scheme 5 by using 2-chloro-3-fluoro-benzaldehyde, ethyl acetoacetate, 1-methyl-1H-imidazole-2-carbonitrile and (S)-morpholine-3-carboxylic acid instead of 2-chloro-4-fluoro-benzaldehyde, methyl acetoacetate, thiazole-2-carbonitrile and (S)-4,4-difluoro-pyrrolidine-2-carboxylic acid. The stereochemistry of Example 97 was determined by comparing its 1H NMR data and HPLC retention time with Example 2.

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 2-Chloro-3-fluorobenzaldehyde (2.5 g) and (R)-(+)-2-methyl-2-propanesulfinamide were dissolved in dichloromethane (50 ml), and then titanium(IV) isopropoxide (23.6 ml) was added. The mixture was heated for three hours under reflux, then poured onto ice (150 g) and stirred vigorously for ten minutes. The mixture was filtered through kieselguhr and the filtrate was extracted with dichloromethane (3×50 ml). The organic phase was dried (Na2SO4), filtered and concentrated under reduced pressure. The product (4 g) was used further without further purification. The mixture was heated for three hours under reflux poured onto ice (150 g) The mixture was filtered through kieselguhr the filtrate was extracted with dichloromethane (3×50 ml) The organic phase was dried (Na2SO4) filtered concentrated under reduced pressure The product (4 g) was used further without further purification

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Compound C-1 was prepared in analogy to compound C by using ethyl acetoacetate and 2-chloro-3-fluorobenzaldehyde instead of methyl acetoacetate and 2-chloro-4-fluorobenzaldehyde.

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of 460 mg of 2-chloro-3-fluorobenzaldehyde, 360 mg of methyl 3-aminocrotonate and 820 mg of 2-(N-benzyl-N-methylamino)ethyl 3-aminocrotonate in 4 ml of 2-propanol was refluxed for 8 hours, and then the solvent was distilled off under reduced pressure. The residue was purified by a column chromatography on silica gel to provide 860 mg of the desired compound (110). was refluxed for 8 hours the solvent was distilled off under reduced pressure The residue was purified by a column chromatography on silica gel

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 2-Chloro-3-fluorobenzaldehyde (2.5 g) and (R)-(+)-2-methyl-2-propanesulfinamide were dissolved in dichloromethane (50 ml), and then titanium(IV) isopropoxide (23.6 ml) was added. The mixture was heated for three hours under reflux, then poured onto ice (150 g) and stirred vigorously for ten minutes. The mixture was filtered through kieselguhr and the filtrate was extracted with dichloromethane (3×50 ml). The organic phase was dried (Na2SO4), filtered and concentrated under reduced pressure. The product (4 g) was used further without further purification. The mixture was heated for three hours under reflux poured onto ice (150 g) The mixture was filtered through kieselguhr the filtrate was extracted with dichloromethane (3×50 ml) The organic phase was dried (Na2SO4) filtered concentrated under reduced pressure The product (4 g) was used further without further purification

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: The title compound was prepared in analogy to Example 2 with Procedure B shown in Scheme 5 by using 2-chloro-3-fluoro-benzaldehyde, ethyl acetoacetate, 1-methyl-1H-imidazole-2-carbonitrile and (S)-morpholine-3-carboxylic acid instead of 2-chloro-4-fluoro-benzaldehyde, methyl acetoacetate, thiazole-2-carbonitrile and (S)-4,4-difluoro-pyrrolidine-2-carboxylic acid. The stereochemistry of Example 97 was determined by comparing its 1H NMR data and HPLC retention time with Example 2.