Methyl 2-amino-4,6-dichlorobenzoate

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: The objective compound was prepared by the same procedure for the intermediate 1, using a 2-(4-methoxy-3-nitro-phenyl)-propionic acid (0.60 g, 2.70 mmol), SOC2 (0.96 mL, 13.0 mmol), and 2-amino-4,6-dichloro-benzoic acid methyl ester (0.77 g, 3.50 mmol). After normal workup, the pure objective compound (0.98 g, 82%) was obtained as white solid by recrystallization (dichloromethane:n-hexane=1:3): m.p 122° C.; 1H NMR (200 MHz, CDCl3) δ 1.60 (d, J=7.2 Hz, 3H, CH3), 3.65-3.84 (m, 4H, CO2CH3 & CH), 7.55 (dd, J=8.8, 2.2 Hz, 1H, ArH), 7.84 (d, J=2.2 Hz, 1H, ArH), 8.44 (d, J=2.0 Hz, 1H, ArH), 9.51 (br s, 1H, NH).

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

実験手順: The objective compound was prepared by the same procedure for the intermediate 1, using a 2-(4-benzyloxy-3-bromo-phenyl)-propionic acid (1.0 g, 3.00 mmol), SOCl2 (1.10 mL, 14.9 mmol), and 2-amino-4,6-dichloro-benzoic acid methyl ester (0.50 g, 2.40 mmol). After normal workup, the pure objective compound (0.91 g, 71%) was obtained as white solid by a flash column chromatography (n-hexane:EtOAc=5:1): 1H NMR (200 MHz, CDCl3) δ 1.53 (s, 3H, CH3), 3.62 (q, J=7.1 Hz, 1H, CH), 3.79 (s, 3H, CO2CH3), 5.16 (s, 2H, CH2Ph), 6.94 (d, J=8.4 Hz, 1H, ArH), 7.15 (d, J=2.30 Hz, 1H, ArH), 7.20 (dd, J=8.6, 2.0 Hz, 1H, ArH), 7.31-7.48 (m, 5H, ArH), 7.54 (d, J=2.4 Hz, 1H, ArH), 8.41 (d, J=2.0 Hz, 1H, ArH), 9.15 (br s, 1H, NH).

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

実験手順: The objective compound was prepared by the same procedure for the intermediate 1, using a 2-(4-benzyloxy-phenyl)-propionic acid (2.70 g, 10.5 mmol), PCl5 (2.30 g, 10.5 mmol), and 2-amino-4,6-dichloro-benzoic acid methyl ester (1.54 g, 7.0 mmol). After normal workup, the pure objective compound (2.90 g, 91%) was obtained as white solid by a flash column chromatography (n-hexane:EtOAc=10:1): 1H NMR (200 MHz, CDCl3) δ 1.59 (d, J=7.0 Hz, 3H, CH3), 3.65-3.76 (m, 1H, CH), 3.76 (s, 3H, CO2CH3), 5.09 (s, 2H, OCH2Ph), 6.93-6.97 (m, 3H, ArH), 7.14 (d, J=1.8 Hz, 1H, ArH), 7.26-7.48 (m, 6H, ArH), 8.42 (d, J=1.8 Hz, 1H, ArH), 9.02 (s, 1H, NH); MS(EI) m/e 458 [M+], 426, 336, 301, 121, 91.

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

実験手順: The objective compound was prepared by the same procedure for the intermediate 1, using a 2-(4-benzyloxy-phenyl)-propionic acid (2.70 g, 10.5 mmol), PCl5 (2.30 g, 10.5 mmol), and 2-amino-4,6-dichloro-benzoic acid methyl ester (1.54 g, 7.0 mmol). After normal workup, the pure objective compound (2.90 g, 91%) was obtained as white solid by a flash column chromatography (n-hexane:EtOAc=10:1): 1H NMR (200 MHz, CDCl3) δ 1.59 (d, J=7.0 Hz, 3H, CH3), 3.65-3.76 (m, 1H, CH), 3.76 (s, 3H, CO2CH3), 5.09 (s, 2H, OCH2Ph), 6.93-6.97 (m, 3H, ArH), 7.14 (d, J=1.8 Hz, 1H, ArH), 7.26-7.48 (m, 6H, ArH), 8.42 (d, J=1.8 Hz, 1H, ArH), 9.02 (s, 1H, NH); MS(EI) m/e 458 [M+], 426, 336, 301, 121, 91.

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

実験手順: The objective compound was prepared by the same procedure for the intermediate 1, using a 2-(4-bromo-phenyl)-propionic acid (11.7 g, 48.3 mmol), SOCl2 (35.0 mL, 480 mmol), and 2-amino-4,6-dichloro-benzoic acid methyl ester (10.1 g, 45.9 mmol). After normal workup, the pure objective compound (9.31 g, 55%) was obtained as white solid by a flash column chromatography (n-hexane:EtOAc=10:1): 1H NMR (200 MHz, CDCl3) δ 1.58 (d, J=7.1 Hz, 3H, CH3), 3.75 (q, J=7.1 Hz, 1H, CH), 3.81 (s, 3H, CO2CH3), 7.15 (d, J=2.0 Hz, 1H, ArH), 7.20-7.53 (m, 4H, ArH), 8.41 (d, J=1.7 Hz, 1H, ArH), 9.16 (br s, 1H, NH).

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

実験手順: The objective compound was prepared by the same procedure for the intermediate 1, using a 2-(4-nitro-phenyl)-propionic acid (1.40 g, 7.17 mmol), SOCl2 (5.1 mL, 71.7 mmol), and 2-amino-4,6-dichloro-benzoic acid methyl ester (1.6 g, 5.74 mmol). After normal workup, the pure objective compound (2.26 g, 99%) was obtained as pale yellow solid by recrystallization (ethyl acetate:ethyl ether=1:5): 1H NMR (200 MHz, CDCl3) δ 1.63 (d, J=7.1 Hz, 3H, CH3), 3.85-3.86 (m, 4H, CO2CH3 & CH), 7.18 (d, J=2.0 Hz, 1H, ArH), 7.54 (d, J=8.7 Hz, 2H, ArH), 8.24 (d, J=8.7 Hz, 2H, ArH), 8.45 (d, J=2.0 Hz, 1H, ArH), 9.59 (br s, 1H, ArH).

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

実験手順: The objective compound was prepared by the same procedure for the intermediate 1, using a 2-(4-nitro-phenyl)-propionic acid (1.40 g, 7.17 mmol), SOCl2 (5.1 mL, 71.7 mmol), and 2-amino-4,6-dichloro-benzoic acid methyl ester (1.6 g, 5.74 mmol). After normal workup, the pure objective compound (2.26 g, 99%) was obtained as pale yellow solid by recrystallization (ethyl acetate:ethyl ether=1:5): 1H NMR (200 MHz, CDCl3) δ 1.63 (d, J=7.1 Hz, 3H, CH3), 3.85-3.86 (m, 4H, CO2CH3 & CH), 7.18 (d, J=2.0 Hz, 1H, ArH), 7.54 (d, J=8.7 Hz, 2H, ArH), 8.24 (d, J=8.7 Hz, 2H, ArH), 8.45 (d, J=2.0 Hz, 1H, ArH), 9.59 (br s, 1H, ArH).

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

実験手順: The objective compound was prepared by the same procedure for the intermediate 1, using a 2-(4-methoxy-phenyl)-propionic acid (1.45 g, 8.0 mmol), SOCl2 (2.09 mL, 24.0 mmol), and 2-amino-4,6-dichloro-benzoic acid methyl ester (1.54 g, 7.0 mmol). After normal workup, the pure objective compound (2.27 g, 85%) was obtained as pale yellow syrup by a flash column chromatography (n-hexane:EtOAc=10:1): 1H NMR (200 MHz, CDCl3) δ 1.56 (d, J=7.0 Hz, 3H, CH3), 3.77 (s, 3H, CO2CH3), 3.81 (s, 3H, OCH3), 3.84-3.95 (m, 1H, CH), 6.83-6.97 (m, 2H, ArH), 7.12 (d, J=2.0 Hz, 1H, ArH), 7.21-7.27 (m, 2H, ArH), 8.41 (d, J=2.0 Hz, 1H, ArH), 8.98 (s, 1H, NH); HRMS(EI) calcd. for C18H17O4NCl2 m/e 381.0536 [M+], found 381.0539.

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

実験手順: A solution of methyl 2-amino-4,6-dichlorobenzoate (1.30 g, 5.91 mM) and dimethyl acetylenedicarboxylate (0.96 g, 6.78 mM) in t-butanol (14 mL) was refluxed for 18 hr under a nitrogen atmosphere. The reaction mixture was cooled to room temperature and potassium t-butoxide (0.76 g, 6.8 mM) was added to the stirred mixture whereupon a precipitate formed. After refluxing for 1.5 hr, the reaction mixture was cooled to room temperature and filtered to separate the precipitated solids. The solids were washed with t-butanol and then dissolved in water. The resulting solution was acidified with 1N H2SO4 and the resulting precipitate was collected, washed thoroughly with water and dried to give the title compound as a light green solid (1.15 g, 59%). An analytical sample was obtained by recrystallization of a portion from toluene to provide the title compound as a light tan solid, mp 109.5°-111° C. (d); MS(CI): 330 (M+H). formed After refluxing for 1.5 hr the reaction mixture was cooled to room temperature filtered to separate the precipitated solids The solids were washed with t-butanol dissolved in water the resulting precipitate was collected washed thoroughly with water dried

反応条件: temp:55.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a stirred solution of sodium hydroxide (0.070 g, 1.8 mM) in methanol (8.5 mL) was added 5,7-dichloro-2H-3,1-benzoxazine-2,4(1H)-dione (4.13 g, 17.8 mM). The reaction mixture was stirred at 55° C. for 2 hr, allowed to cool to room temperature and concentrated. The residue was diluted with water and the resulting mixture extracted with ethyl acetate. The combined extracts were dried (MgSO4), filtered and concentrated to leave the methyl 2-amino-4,6-dichlorobenzoate (3.61 g, 92.1%) as a brown solid; MS(CI): 220 (M+H). to cool to room temperature concentrated The residue was diluted with water the resulting mixture extracted with ethyl acetate The combined extracts were dried (MgSO4) filtered concentrated