methyl 2-(3-aminophenyl)acetate

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:

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:

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

実験手順: To a solution of methyl(3-aminophenyl)acetate (25 g, 140 mmol) in 250 mL anhydrous DCM was added DIEA (28.5 mL, 155 mmol) and the resulting solution cooled to 0° C. and set under nitrogen atmosphere. To this cooled solution was then added benzyl chloroformate (21.1 mL, 148 mmol) and the resulting mixture stirred overnight allowing to warm to room temperature. The reaction was washed with 1 M HCl, water, and then brine. The organic layer was dried over sodium sulfate, filtered and concentrated under vacuum. No further purification was necessary and the material (44 g, 99%) was used as is for the next step reaction. LC-MS: m/z (ES) 314 (MH)+, 336 (MNa)+. to warm to room temperature The reaction was washed with 1 M HCl, water The organic layer was dried over sodium sulfate filtered concentrated under vacuum No further purification as is for the next step reaction

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

実験手順: Prepared in an essentially similar fashion from methyl 3-aminophenyl-acetate (111 g, 0.67 mole) and potassium methanethiolate (2.68 mole) to give 3-methylthiophenylacetic acid (21.0 g). Mp=76-77° C., 1H NMR (DMSO-d6, 200 MHz) δ: 2.44 (s, 3H, SCH3), 3.53 (s, 2H, ArCH2), 7.02-7.28 (m, 4H, Ar), 12.30 (br s, 1H, CO2H). Mass spectrum (CI—CH4): 183 (M+1, 100%). (Lit. ref.: Plant Physiol 42(11) 2596-1600 (1967).

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

実験手順: To a solution of methyl 3-aminophenylacetate (102 g, 0.62 mole) in 1N HCl (1600 ml) cooled in an ice bath was added NaNO2 (42.7 g, 0.62 mole) portionwise and the solution stirred for 20 minutes. A solution of potassium ethanethiolate was prepared by adding ethanethiol (202 ml, 2.73 mole) dropwise over 10 minutes to a solution of 87.5% KOH (159 g, 2.48 mole) in water (1.2 l ) at 0° C. The diazonium salt solution was then added via cannula to the solution of potassium ethanethiolate and the reaction mixture was stirred 30 minutes in an ice bath. Diethyl ether (˜1.5 l ) was added and the mixture was stirred 1.5 hours at room temperature. The ether layer was separated, the aqueous phase further extracted with diethyl ether (3×700 ml), and the combined ether solutions concentrated. The residue was eluted from silica gel with ethyl acetate:hexane (1:19) to give a mixture of methyl 3-ethylthiophenylacetate 1H NMR (DMSO-d6, 200 MHz) δ: 1.21 (t, J=7 Hz, 3H, ethyl CH3), 2.95 CH2), 3.60 (s, 3H, OCH3), 3.65 (s, 2H, ArCH2), 7.02-7.44 (m, Ar), and methyl phenylacetate (85.9 g). The esters (84 g) were hydrolyzed in a solution of methanol (500 ml) and 6.25 N NaOH(100 ml) stirred overnight at room temperature. The solution was concentrated in vacuo to remove the methanol, the remaining solution acidified with concentrated HCl and the resulting solid was extracted into diethyl ether. The ether solution was washed with brine (3×100 ml), dried (Na2SO4) and concentrated. Vacuum distillation (0.5 mm Hg) gave a distillate (100-115° C.) of phenylacetic acid and a residue of 3-ethylthiophenylacetic acid. The residue in the flask solidified upon cooling to give 3-ethylthiophenylacetic acid (49.8 g). Mp=49-51° C. 1H NMR (DMSO-d6, 200 MHz) δ: 1.21 (t, J=7 Hz, 3H, CH3), 2.95 (q, J=7 Hz, 2H, SCH2), 3.54 (s, 2H, ArCH), 7.01-7.28 (m, 4H, Ar), 12.33 (br s, 1H, CO2H). Mass spectrum (CI—CH4): 197 (M+1, 100%). the reaction mixture was stirred 30 minutes in an ice bath the mixture was stirred 1.5 hours at room temperature The ether layer was separated the aqueous phase further extracted with diethyl ether (3×700 ml) the combined ether solutions concentrated The residue was eluted from silica gel with ethyl acetate:hexane (1:19) to give stirred overnight at room temperature The solution was concentrated in vacuo to remove the methanol the resulting solid was extracted into diethyl ether The ether solution was washed with brine (3×100 ml) dried (Na2SO4) concentrated Vacuum distillation (0.5 mm Hg)

反応条件: temp:0.00; pressure:0.00; stir: