methyl 2-(2,6-dichlorophenyl)acetate

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:; See reaction.notes.procedure_details.

Procedure: (2,6-Dichlorophenyl)acetic acid (2.55 g) was dissolved in anhydrous MeOH (60 mL) and HCl (gas) was passed through the mixture and the resulting solution was stirred at room temperature for 18 h. The solvent was then evaporated to give (2,6-dichlorophenyl)acetic acid methyl ester (2.7 g). The solvent was then evaporated

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

Procedure: (2,6-Dichlorophenyl)acetic acid (2.55 g) was dissolved in anhydrous MeOH (60 mL) and HCl (gas) was passed through the mixture and the resulting solution was stirred at room temperature for 18 h. The solvent was then evaporated to give (2,6-dichlorophenyl)acetic acid methyl ester (2.7 g). The solvent was then evaporated

Conditions: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of N-isopropylcyclohexylamine (1.44 g, 10.0 mmol) (Aldrich) in dry tetrahydrofuran (20 mL) was added n-butyllithium (2.5 M in hexanes, 4.0 mL, 10.0 mmol) (Aldrich) at −78° C. under argon. After 30 minutes, a solution of 2,6-dichloro-phenylacetic acid methyl ester (2.19 g, 10.0 mmol) (TCI-US) in tetrahydrofliran (5 mL) was added by injection via a syringe and the reaction mixture was stirred at −78° C. for another 30 minutes. To this reaction mixture was added a solution of 2,4-dichloro-5-iodomethyl-pyrimidine (1.45 g, 5.0 mmol) (from Example 1c supra) in tetrahydrofuran (5 mL) at −78° C. and the reaction mixture was stirred at the same temperature for 1 hour then slowly allowed to warm up to −30° C. and stirred for 10 minutes. The reaction mixture was diluted with ethyl acetate (100 mL) and successively washed with saturated aqueous ammonium chloride solution (100 mL), water (50 mL) and brine (50 mL), dried over anhydrous sodium sulfate, filtered, and concentrated in vacuo. The residue was purified by flash column chromatography to give 2-(2,6-dichloro-phenyl)-3-(2,4-dichloro-pyrimidin-5-yl)-propionic acid methyl ester as a colorless oil. (Yield 1.57 g, 82.6%). the reaction mixture was stirred at the same temperature for 1 hour to warm up to −30° C. stirred for 10 minutes successively washed with saturated aqueous ammonium chloride solution (100 mL), water (50 mL) and brine (50 mL) dried over anhydrous sodium sulfate filtered concentrated in vacuo The residue was purified by flash column chromatography

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

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

Procedure: (2,6-Dichlorophenyl)acetic acid (2.55 g) was dissolved in anhydrous MeOH (60 mL) and HCl (gas) was passed through the mixture and the resulting solution was stirred at room temperature for 18 h. The solvent was then evaporated to give (2,6-dichlorophenyl)acetic acid methyl ester (2.7 g). The solvent was then evaporated

Conditions: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of N-isopropylcyclohexylamine (1.44 g, 10.0 mmol) (Aldrich) in dry tetrahydrofuran (20 mL) was added n-butyllithium (2.5 M in hexanes, 4.0 mL, 10.0 mmol) (Aldrich) at −78° C. under argon. After 30 minutes, a solution of 2,6-dichloro-phenylacetic acid methyl ester (2.19 g, 10.0 mmol) (TCI-US) in tetrahydrofliran (5 mL) was added by injection via a syringe and the reaction mixture was stirred at −78° C. for another 30 minutes. To this reaction mixture was added a solution of 2,4-dichloro-5-iodomethyl-pyrimidine (1.45 g, 5.0 mmol) (from Example 1c supra) in tetrahydrofuran (5 mL) at −78° C. and the reaction mixture was stirred at the same temperature for 1 hour then slowly allowed to warm up to −30° C. and stirred for 10 minutes. The reaction mixture was diluted with ethyl acetate (100 mL) and successively washed with saturated aqueous ammonium chloride solution (100 mL), water (50 mL) and brine (50 mL), dried over anhydrous sodium sulfate, filtered, and concentrated in vacuo. The residue was purified by flash column chromatography to give 2-(2,6-dichloro-phenyl)-3-(2,4-dichloro-pyrimidin-5-yl)-propionic acid methyl ester as a colorless oil. (Yield 1.57 g, 82.6%). the reaction mixture was stirred at the same temperature for 1 hour to warm up to −30° C. stirred for 10 minutes successively washed with saturated aqueous ammonium chloride solution (100 mL), water (50 mL) and brine (50 mL) dried over anhydrous sodium sulfate filtered concentrated in vacuo The residue was purified by flash column chromatography

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

Procedure: To sodium ethoxide [prepared by reacting sodium (60 mg, 2.61 mmol) and anhydrous ethanol (5 ml)] benzylguanidine hydrochloride (580 mg, 3.12 mmol) was added and refluxed in an oilbath for 1 hour. The reaction mixture was cooled to room temperature and insoluble materials filtered. Methyl 2,6-dichlorophenylacetate (285 mg, 1.3 mmol) (CH3(C═O)CH2(2,6,-di-ClC6H3) was added to the filtrate and refluxed for 2 hours. After cooling to room temperature the reaction mixture was concentrated and converted to the hydrochloride salt by the addition of hydrogen chloride (1M in ether) to provide 310 mg of N-(2,6-dichlorophenylacetyl)-N′-benzylguanidine hydrochloride as a white solid, purity 89.3% (HPLC); 1H-NMR (CD3OD) δ 4.38 (s, 4H, CH2), 7.32–7.41 (m, 8H, Ar). refluxed in an oilbath for 1 hour insoluble materials filtered refluxed for 2 hours After cooling to room temperature the reaction mixture was concentrated converted to the hydrochloride salt by the addition of hydrogen chloride (1M in ether)

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

Procedure: (2,6-Dichlorophenyl)acetic acid (2.55 g) was dissolved in anhydrous MeOH (60 mL) and HCl (gas) was passed through the mixture and the resulting solution was stirred at room temperature for 18 h. The solvent was then evaporated to give (2,6-dichlorophenyl)acetic acid methyl ester (2.7 g). The solvent was then evaporated