2-amino-4-methylphenol

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: 2-(2-Amino-4-methyl-phenoxymethyl)-morpholine-4-carboxylic acid tert-butyl ester (0.087 g, 0.270 mmol) was prepared from 2-amino-4-methyl-phenol according to methods of Compound 3, Steps 1 and 2 using 2-hydroxymethyl-morpholine-4-carboxylic acid tert-butyl ester (prepared according to the procedure for Compound 2, Step 1 using the corresponding acid) and 4-methyl-2-nitro-phenol. It was combined with triphosgene (0.029 g, 0.10 mmol), toluene (2 mL) and Hunig's base (0.15 mL, 0.86 mmol), and stirred at room temperature for 25 min. The suspension then was transferred through a cannula to a cold solution (−78° C.) containing 5-amino-pyrazine-2-carbonitrile (0.032 g, 0.27 mmol), and lithium bis(trimethylsilyl)amide (0.27 mmol) in THF (1 mL), which had been stirring at −78° C. for 30 min. The reaction was allowed to warm, then was stirred for 16 h at room temperature. A precipitate formed and was collected by filtration to yield the desired product (0.043 g). prepared then was transferred through a cannula to a cold solution (−78° C.) had been stirring at −78° C. for 30 min to warm was stirred for 16 h at room temperature A precipitate formed was collected by filtration

Conditions: temp:180.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 2-Amino-4-methylphenol (400 mg) and 4-piperidinecarboxylic acid (420 mg) were mixed with polyphosphoric acid (2 g) and stirred with heating at 180° C. for 2 hours. After cooling to room temperature, the reaction was stopped by adding water. The filtrate was adjusted to pH 12 with 50% potassium hydroxide aqueous solution and then extracted with methylene chloride. The organic layer was washed with saturated brine and dried with magnesium sulfate, and then the solvent was evaporated under a reduced pressure to obtain the title compound 2-(4-piperidyl)-5-methylbenzoxazole (586 mg). After cooling to room temperature extracted with methylene chloride The organic layer was washed with saturated brine dried with magnesium sulfate the solvent was evaporated under a reduced pressure

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

Procedure: 1.075 g of methyl (3-cyano-4,5-dihydroxyphenyl)-glyoxylate and 0.60 g of 2-amino-p-cresol are stirred at 120° for 70 minutes in 2 ml of dimethylformamide. The mixture is subsequently cooled to room temperature and diluted with 15 ml of water. The precipitate is filtered and dried in a water-jet vacuum at 80° for 6 hours. After recrystallization from acetonitrile there is obtained 2,3-dihydroxy-5-(6-methyl-2-oxo-2H-1,4-benzoxazin-3-yl)-benzonitrile of m.p. 278°-280°. The precipitate is filtered dried in a water-jet vacuum at 80° for 6 hours After recrystallization from acetonitrile

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

Procedure: 1.075 g of methyl (3-cyano-4,5-dihydroxyphenyl)-glyoxylate and 0.60 g of 2-amino-p-cresol are stirred at 120° for 70 minutes in 2 ml of dimethylformamide. The mixture is subsequently cooled to room temperature and diluted with 15 ml of water. The precipitate is filtered and dried in a water-jet vacuum at 80° for 6 hours. After recrystallization from acetonitrile there is obtained 2,3-dihydroxy-5-(6-methyl-2-oxo-2H-1,4-benzoxazin-3-yl)-benzonitrile of m.p. 278°-280°. The precipitate is filtered dried in a water-jet vacuum at 80° for 6 hours After recrystallization from acetonitrile

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

Procedure: A solution of 2-amino-p-cresol (9.8 g) and 2-formylbenzonitrile (10.5 g) in ethanol (160 ml) was allowed to stand for 20 hours. The precipitated solid was filtered off and washed with ethanol (30 ml) to give 2-hydroxy-5-methyl-N-(2-cyanobenzylidene)aniline (C) (3.1 g), m.p. 135°-138° C.; NMR: 2.35(s, 3H), 6.95(d, 1H), 7.1(dd, 1H), 7.2(s & br s, 2H), 7.55(dt, 1H), 7.7(dt, 1H), 7.8(dd, 1H) 8.1(dd, 1H), 8.9(s, 1H). The precipitated solid was filtered off washed with ethanol (30 ml)

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

Procedure: A solution of 2-amino-p-cresol (9.8 g) and 2-formylbenzonitrile (10.5 g) in ethanol (160 ml) was allowed to stand for 20 hours. The precipitated solid was filtered off and washed with ethanol (30 ml) to give 2-hydroxy-5-methyl-N-(2-cyanobenzylidene)aniline (C) (3.1 g), m.p. 135°-138° C.; NMR: 2.35(s, 3H), 6.95(d, 1H), 7.1(dd, 1H), 7.2(s & br s, 2H), 7.55(dt, 1H), 7.7(dt, 1H), 7.8(dd, 1H) 8.1(dd, 1H), 8.9(s, 1H). The precipitated solid was filtered off washed with ethanol (30 ml)

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

Procedure: A solution of 2-amino-p-cresol (7.4 g) and methyl 2-formylbenzoate (obtained as described in J. Chem. Soc. (C), 1969, 1818) (9.8 g) in ethanol (120 ml) was heated under reflux for 2 hours. The solvent was removed by evaporation and the residue recrystallised from hexane to give 2-hydroxy-5-methyl-N-(2-methoxycarbonylbenzylidene)aniline (B) (12.3 g), m.p. 82°-83° C; NMR: 2.35 (s, 3H), 4.0(s, 3H), 6.9(d, 1H), 7.0(d, 1H), 7.05(br s, 1H), 7.15(d, 1H), 7.5-7.7(m, 2H), 7.95(dd, 1H), 8.2(dd, 1H), 9.45(s, 1H). under reflux for 2 hours The solvent was removed by evaporation the residue recrystallised from hexane

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

Procedure: A solution of 2-amino-p-cresol (7.4 g) and methyl 2-formylbenzoate (obtained as described in J. Chem. Soc. (C), 1969, 1818) (9.8 g) in ethanol (120 ml) was heated under reflux for 2 hours. The solvent was removed by evaporation and the residue recrystallised from hexane to give 2-hydroxy-5-methyl-N-(2-methoxycarbonylbenzylidene)aniline (B) (12.3 g), m.p. 82°-83° C; NMR: 2.35 (s, 3H), 4.0(s, 3H), 6.9(d, 1H), 7.0(d, 1H), 7.05(br s, 1H), 7.15(d, 1H), 7.5-7.7(m, 2H), 7.95(dd, 1H), 8.2(dd, 1H), 9.45(s, 1H). under reflux for 2 hours The solvent was removed by evaporation the residue recrystallised from hexane

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 2-amino-4-methylphenol (5 g, 40.6 mmol) and pyridine (5 ml, 62 mmol) in methylene chloride (70 ml) was added dropwise a solution of acryloyl chloride (4 ml, 50 mmol) in methylene chloride (30 ml) under ice-cooling. The reaction mixture was stirred at 0° C. for 2 hours. To the reaction mixture was added water, and the mixture was stirred at room temperature for 30 minutes, extracted with methylene chloride, washed with a saturated aqueous solution of sodium hydrogencarbonate and saturated brine and dried over anhydrous magnesium sulfate. The solvent was distilled off, and thus obtained brown oil was purified by column chromatography on silica gel to give a pale yellow prismatic crystals. Yield 1.55 g (22%). cooling the mixture was stirred at room temperature for 30 minutes extracted with methylene chloride washed with a saturated aqueous solution of sodium hydrogencarbonate and saturated brine dried over anhydrous magnesium sulfate The solvent was distilled off thus obtained brown oil was purified by column chromatography on silica gel to give a pale yellow prismatic crystals

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

Procedure: To 2-amino-p-cresol (8.01 g, 65 mmol) was added formic acid (5.98 g, 130 mmol) and the mixture was refluxed for 1 hour. The reaction mixture was allowed to stand for cooling. After the addition of ethyl acetate, the mixture was poured into ice-cold water. The aqueous layer was neutralized with a saturated aqueous solution of sodium hydrogencarbonate and extracted with ethyl acetate. The organic layer was washed with a saturated aqueous solution of sodium hydrogencarbonate and saturated brine, dried over anhydrous magnesium sulfate and evaporated. The residue was purified by column chromatography on silica gel and recrystallized from ethyl acetate-hexane to give the title compound (1). Yield 8.59 g (88%). the mixture was refluxed for 1 hour for cooling the mixture was poured into ice-cold water extracted with ethyl acetate The organic layer was washed with a saturated aqueous solution of sodium hydrogencarbonate and saturated brine dried over anhydrous magnesium sulfate evaporated The residue was purified by column chromatography on silica gel recrystallized from ethyl acetate-hexane