4-chloro-2-methylbenzaldehyde

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

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

実験手順: A mixture of 4-chloro-2-methylbenzaldehyde (3.5 g, 22.6 mmol) and aniline (2.11 g, 22.6 mmol) in toluene (40 ml) was heated at reflux in a Dean-Stark apparatus for 1 hour. The mixture was cooled and evaporated in vacuo to leave an oily residue. The residue was redissolved in ether, washed with 5% sodium bicarbonate solution. The organic phase was separated, dried over MgSO4 and filtered. The filtrate was concentrated in vacuo to afford an oily residue which was purified by distillation via a Kugelrohr apparatus (oven temperature 160° C., 0.5 mm) to provide the title compound (4.0 g, 7.4 mmol, 77%) as a viscous oil; pmr (CDCl3)δ2.5(3H, s), 6.3-7.5(7H,m), 7.95(H, d), 8.6(H,s). was heated at reflux in a Dean-Stark apparatus for 1 hour The mixture was cooled evaporated in vacuo to leave an oily residue washed with 5% sodium bicarbonate solution The organic phase was separated dried over MgSO4 filtered The filtrate was concentrated in vacuo to afford an oily residue which was purified by distillation via a Kugelrohr apparatus (oven temperature 160° C., 0.5 mm)

反応条件: temp:-23.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution of n-butyllithium in hexane (30.4 ml, 2.5M) was added dropwise with stirring under nitrogen to a solution of N,N,N'-trimethylethylenediamine (7.9 g) in dry THF (150 ml) at -15 to -20° C. After the addition the mixture was stirred at -23° C. for 15 minutes and then 4-chlorobenzaldehyde (10.0 g) was added dropwise at -15 to -20° C. After the addition the mixture was stirred at -23° C. for 15 minutes and then more n-butyllithium in hexane (85.4 ml, 2.5M) was added dropwise at -15° C. The mixture was stirred at -23° C. for 3 hours, cooled to -40° C. and iodomethane (60.6 g) added at -40° to -20° C. After the addition, the mixture was stirred at -40° C. for 5 minutes and then allowed to warm up to ambient temperature and then stirred at that temperature for 30 minutes. The mixture was carefully poured into ice cold 10% hydrochloric acid (2 1) and left standing for 64 hours. The mixture was extracted with diethyl ether to give an oil which was distilled twice under vacuum to give 4-chloro-2-methylbenzaldehyde, b.p. 105°-110° (15 mmHg) which was sufficiently pure for synthetic use in Example 40. After the addition the mixture After the addition the mixture was stirred at -23° C. for 15 minutes The mixture was stirred at -23° C. for 3 hours cooled to -40° C. After the addition the mixture was stirred at -40° C. for 5 minutes to warm up to ambient temperature stirred at that temperature for 30 minutes left standing for 64 hours The mixture was extracted with diethyl ether to give an oil which was distilled twice under vacuum

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

実験手順: A mixture of 4-chloro-2-methylbenzaldehyde (1.56 g, 10.1 mmol), methylamine hydrochloride (0.44 g, 6.5 mmol), and sodium acetate (0.53 g, 6.5 mmol) in nitromethane (4 mL) was vigorously stirred at ambient temperature for 24 hours. The reaction mixture was diluted with water (20 mL) and dichloromethane (40 mL). The organic layer was dried over sodium sulfate and evaporated to afford 4-chloro-2-methyl-1-(2-nitrovinyl)benzene as a light brown solid (1.87 g, 94% yield). The organic layer was dried over sodium sulfate evaporated

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

実験手順: A mixture of 4-chloro-2-methylbenzaldehyde (1.56 g, 10.1 mmol), methylamine hydrochloride (0.44 g, 6.5 mmol), and sodium acetate (0.53 g, 6.5 mmol) in nitromethane (4 mL) was vigorously stirred at ambient temperature for 24 hours. The reaction mixture was diluted with water (20 mL) and dichloromethane (40 mL). The organic layer was dried over sodium sulfate and evaporated to afford 4-chloro-2-methyl-1-(2-nitrovinyl)benzene as a light brown solid (1.87 g, 94% yield). The organic layer was dried over sodium sulfate evaporated

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

実験手順: A mixture of 4-chloro-2-methylbenzaldehyde (3.5 g, 22.6 mmol) and aniline (2.11 g, 22.6 mmol) in toluene (40 ml) was heated at reflux in a Dean-Stark apparatus for 1 hour. The mixture was cooled and evaporated in vacuo to leave an oily residue. The residue was redissolved in ether, washed with 5% sodium bicarbonate solution. The organic phase was separated, dried over MgSO4 and filtered. The filtrate was concentrated in vacuo to afford an oily residue which was purified by distillation via a Kugelrohr apparatus (oven temperature 160° C., 0.5 mm) to provide the title compound (4.0 g, 7.4 mmol, 77%) as a viscous oil; pmr(CDCl3) δ 2.5 (3H, s), 6.3~7.5 (7H, m), 7.95 (H, d), 8.6 (H, s). was heated at reflux in a Dean-Stark apparatus for 1 hour The mixture was cooled evaporated in vacuo to leave an oily residue washed with 5% sodium bicarbonate solution The organic phase was separated dried over MgSO4 filtered The filtrate was concentrated in vacuo to afford an oily residue which was purified by distillation via a Kugelrohr apparatus (oven temperature 160° C., 0.5 mm)

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

実験手順: 5-Methyl-2,4-dioxo-hexanoic acid ethyl ester (5.6 g, 36.4 mmol) was added to a solution of 4-methoxybenzyl amine (5 g, 36.4 mmol) in acetic acid (40 mL). The mixture was stirred for 10 min at rt. 4-Chloro-2-methylbenzaldehyde (6.77 g, 36.4 mmol) was added. The reaction mixture was heated to 120° C., stirred at this temperature overnight, allowed to cool to rt and diluted with acetonitrile. The resulting precipitate was collected by vacuum filtration and dried to provide 11 g of the title compound. tR: 1.80 min (LC-MS 2); ESI-MS: 414 [M+H]+ (LC-MS 2). The reaction mixture was heated to 120° C. stirred at this temperature overnight to cool to rt The resulting precipitate was collected by vacuum filtration dried

反応条件: temp:120.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of 3-amino-5-chloro-benzonitrile (2.4 g, 15.7 mmol), 4-chloro-2-methyl-benzaldehyde (2.4 g, 15.7 mmol) and 5-methyl-2,4-dioxo-hexanoic acid ethyl ester (2.9 g, 15.7 mmol) in acetic acid (15 mL) was stirred at 120° C. for 16 h. The reaction mixture was allowed to cool to rt, concentrated, diluted with acetonitrile (15 mL), and stirred for 4 h at rt. The resulting precipitate was collected by vacuum filtration and dried to afford 1.8 g of the title compound. tR: 6.50 min (HPLC 2); ESI-MS: 429 [M+H]+ (LC-MS 2); Rf=0.27 (hexane/EtOAc, 1:1). to cool to rt concentrated diluted with acetonitrile (15 mL) stirred for 4 h at rt The resulting precipitate was collected by vacuum filtration dried

反応条件: temp:120.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of 3-amino-5-chloro-benzonitrile (2.4 g, 15.7 mmol), 4-chloro-2-methyl-benzaldehyde (2.4 g, 15.7 mmol) and 5-methyl-2,4-dioxo-hexanoic acid ethyl ester (2.9 g, 15.7 mmol) in acetic acid (15 mL) was stirred at 120° C. for 16 h. The reaction mixture was allowed to cool to rt, concentrated, diluted with acetonitrile (15 mL), and stirred for 4 h at rt. The resulting precipitate was collected by vacuum filtration and dried to afford 1.8 g of the title compound. tR: 6.50 min (HPLC 2); ESI-MS: 429 [M+H]+ (LC-MS 2); Rf=0.27 (hexane/EtOAc, 1:1). to cool to rt concentrated diluted with acetonitrile (15 mL) stirred for 4 h at rt The resulting precipitate was collected by vacuum filtration dried

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

実験手順: A mixture of 3-chloro-2-fluoro-aniline (0.70 g, 4.8 mmol), 4-chloro-2-methyl-benzaldehyde (0.74 g, 4.8 mmol) and the sodium salt of 5-methyl-2,4-dioxo-hexanoic acid ethyl ester (1.0 g, 4.8 mmol) in acetic acid (6 mL) was refluxed for 3 h. The reaction mixture was diluted with water and extracted twice with ethyl acetate. The combined organic extracts were washed with brine, dried (Na2SO4), filtered, and concentrated. The residue was purified by silica gel column chromatography (CH2Cl2/MeOH, 1:0→9:1), followed by crystallization from EtOAc/hexane, to provide 426 mg of the title compound. tR: 5.47 min (HPLC 1); ESI-MS: 422 [M+H]+ (LC-MS 1). extracted twice with ethyl acetate The combined organic extracts were washed with brine dried (Na2SO4) filtered concentrated The residue was purified by silica gel column chromatography (CH2Cl2/MeOH, 1:0→9:1) followed by crystallization from EtOAc/hexane

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

実験手順: A mixture of 3-chloro-2-fluoro-aniline (0.70 g, 4.8 mmol), 4-chloro-2-methyl-benzaldehyde (0.74 g, 4.8 mmol) and the sodium salt of 5-methyl-2,4-dioxo-hexanoic acid ethyl ester (1.0 g, 4.8 mmol) in acetic acid (6 mL) was refluxed for 3 h. The reaction mixture was diluted with water and extracted twice with ethyl acetate. The combined organic extracts were washed with brine, dried (Na2SO4), filtered, and concentrated. The residue was purified by silica gel column chromatography (CH2Cl2/MeOH, 1:0→9:1), followed by crystallization from EtOAc/hexane, to provide 426 mg of the title compound. tR: 5.47 min (HPLC 1); ESI-MS: 422 [M+H]+ (LC-MS 1). extracted twice with ethyl acetate The combined organic extracts were washed with brine dried (Na2SO4) filtered concentrated The residue was purified by silica gel column chromatography (CH2Cl2/MeOH, 1:0→9:1) followed by crystallization from EtOAc/hexane