methyl 2-formylbenzoate

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

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

Procedure: To a solution of N-(2-bromo-5-chloro-pyridin-3-yl)-4-chloro-N-methoxymethyl-3-trifluoromethyl-benzenesulfonamide (250 mg, 0.50 mmol) in THF (3.0 mL) under nitrogen atmosphere at 0° C. was added isopropylmagnesium chloride (0.60 mL, 1.2 mmol, 2 M in THF). The mixture was then stirred for 30 min at 0° C. and 2-formyl-benzoic acid methyl ester (164 mg, 1.0 mmol) was added. The aqueous layer was stirred at room temperature overnight, quenched with saturated aqueous ammonium chloride, and followed by sodium bicarbonate to pH ˜6. The mixture was extracted with ethyl acetate, dried, and concentrated to provide 4-chloro-N-[5-chloro-2-(3-oxo-1,3-dihydro-isobenzofuran-1-yl)-pyridin-3-yl]-N-methoxymethyl-3-trifluoromethyl-benzenesulfonamide. The crude residue was used directly in the next step. The aqueous layer was stirred at room temperature overnight quenched with saturated aqueous ammonium chloride The mixture was extracted with ethyl acetate dried concentrated

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

Procedure: To a solution of 1-Boc-3-aminoazetidine 1a (1.0 g, 5.8 mmol) and methyl 2-formylbenzoate 2a (0.95 g, 5.8 mmol) in 1,2-dichloroethane (30 mL) and acetic acid (1.5 mL) was added Na(OAc)3BH (1.29 g, 6.08 mmol) at room temperature. The reaction was stirred for 5.5 h. It was quenched with aq. NaHCO3, and the resulting mixture was extracted with CH2Cl2. The organic solution was dried over Na2SO4 and concentrated. Purification by flash column chromatography (silica gel, 40% EtOAc/heptane) gave compound 2b (1.46 g). It was quenched with aq. NaHCO3 the resulting mixture was extracted with CH2Cl2 The organic solution was dried over Na2SO4 concentrated Purification by flash column chromatography (silica gel, 40% EtOAc/heptane)

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

Procedure: A mixture containing 5.0 g methyl 2-formylbenzoate [C. Brown and M. V. Sargent, J. Chem. Soc. (C), 1818 (1969)] and 4.0 g 2-amino-2,3-dimethylbutyramide and 50 mg p-toluenesulfonic acid in 100 mL toluene is heated under reflux under a Dean-Stark water separator for three hours. The mixture is filtered and concentrated in vacuo. The residue crystallizes on standing and is recrystallized from etherhexane to give analytically pure methyl o-[N-(1-carbamoyl-1,2-dimethylpropyl)formimidoyl]benzoate, mp 79°-80.5° C. is heated The mixture is filtered concentrated in vacuo The residue crystallizes on standing is recrystallized from etherhexane

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

Procedure: 5 cc of methylmercaptan is added to a solution of methyl 2-formylbenzoate (3.6 g) and 3-(4-phenyl-1,2,3,6-tetrahydro-1-pyridyl)-1-aminopropane (9.6 g)in tetrahydrofuran (255 cc) in an autoclave, at a temperature close to -20° C. in the course of 5 minutes. The solution is heated to a temperature close to 60° C. for 4 hours. After cooling to a temperature close to 20° C., the solution is poured into 1N sodium hydroxide (300 cc) and washed with distilled water (3×500 cc). The organic extract is dried over anhydrous magnesium sulphate, filtered and concentrated to dryness under reduced pressure (20 mm Hg; 2.7 kPa) at 40° C. The residue obtained is dissolved in ethyl acetate (20 cc) and poured onto silica (750 g) contained in a column of 8 cm diameter. Elution is carried out with ethyl acetate. The first 3400 cc are eliminated and the next 3100 cc are evaporated to dryness under reduced pressure (20 mm Hg; 2.7 kPa) at 40° C. The residue obtained is dissolved in methyl ethyl ketone (70 cc). A solution of oxalic acid (1.7 g) in methyl ethyl ketone (20 cc) is added and agitation continued for 1 hour at a temperature close to 20° C. The precipitate formed is separated by filtration. 5.9 g of 3-methylthio-2-[3-(4-phenyl-1,2,3,6-tetrahydro-1-pyridyl)propyl]-1-isoindolinone oxalate are thus obtained, melting at 169° C. close to -20° C. in the course of 5 minutes The solution is heated to a temperature close to 60° C. for 4 hours After cooling to a temperature close to 20° C. washed with distilled water (3×500 cc) The organic extract is dried over anhydrous magnesium sulphate filtered concentrated to dryness under reduced pressure (20 mm Hg; 2.7 kPa) at 40° C The residue obtained poured onto silica (750 g) Elution the next 3100 cc are evaporated to dryness under reduced pressure (20 mm Hg; 2.7 kPa) at 40° C The residue obtained close to 20° C The precipitate formed is separated by filtration

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

Procedure: To a solution of methyl 2-formylbenzoate (15 g) and tosylmethyl isocyanide (18 g) in methanol (250 mL) was added potassium carbonate (15 g), and the mixture was heated under reflux for 16 hr. The reaction mixture was concentrated under reduced pressure, the residue was diluted with ethyl acetate, and the mixture was washed with water and saturated brine. The extract was dried over anhydrous sodium sulfate, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate/petroleum ether) to give the title compound (4.0 g). the mixture was heated under reflux for 16 hr The reaction mixture was concentrated under reduced pressure the residue was diluted with ethyl acetate the mixture was washed with water and saturated brine The extract was dried over anhydrous sodium sulfate the solvent was evaporated under reduced pressure The residue was purified by silica gel column chromatography (ethyl acetate/petroleum ether)