2-(2-methoxyphenyl)acetyl chloride

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: 4.2 cm3 of triethylamine and then 2.4 g of (2-methoxyphenyl)acetic acid chloride in 50 cm3 of dichloromethane are added to a solution of 4.5 g of (3aRS,4RS,5RS,7aRS)-7,7-diphenyl-4-(2-methoxyphenyl)perhydroisoindole-4,5-diol hydrochloride in 100 cm3 of dichloromethane, cooled to 0° C. The reaction mixture is stirred at room temperature for 90 minutes; it is washed with twice 10 cm3 of water, and is dried over magnesium sulphate and concentrated to dryness under reduced pressure (2.7 kPa). The solid which has crystallized is taken up in. 100 cm3 of diisopropyl ether and then filtered off and washed with 50 cm3 of a saturated solution of sodium bicarbonate and then 50 cm3 of diisopropyl ether. 4.35 g of (3aRS,4RS,5RS,7aRS)-7,7-diphenyl-4-(2-methoxyphenyl)-2-(2-methoxyphenyl)- acetylperhydroisoindole-4,5-diol are obtained in the form of a light beige solid which melts at 278° C. it is washed with twice 10 cm3 of water is dried over magnesium sulphate concentrated to dryness under reduced pressure (2.7 kPa) The solid which has crystallized 100 cm3 of diisopropyl ether and then filtered off washed with 50 cm3 of a saturated solution of sodium bicarbonate

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

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

Procedure: To a mixed solution of acetone (300 ml) and a 6% aqueous potassium carbonate solution (200 ml) there were added 10.2 g (67 mmol) of methyl ester of anthranilic acid. 12.5 g (67 mmol) of 2-Methoxyphenylacetic acid chloride were added dropwise under cooling thereto and the resulting reaction mixture was stirred at room temperature for 4 hours. The resulting precipitates were collected by filtration to obtain 15.7 g (yield 78%) of N-(2-methoxyphenylacetyl)-anthranilic acid methyl ester. under cooling the resulting reaction mixture The resulting precipitates were collected by filtration

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

Procedure: To a mixed solution of acetone (300 ml) and a 6% aqueous potassium carbonate solution (200 ml) there were added 10.2 g (67 mmol) of methyl ester of anthranilic acid. 12.5 g (67 mmol) of 2-Methoxyphenylacetic acid chloride were added dropwise under cooling thereto and the resulting reaction mixture was stirred at room temperature for 4 hours. The resulting precipitates were collected by filtration to obtain 15.7 g (yield 78%) of N-(2-methoxyphenylacetyl)-anthranilic acid methyl ester. under cooling the resulting reaction mixture The resulting precipitates were collected by filtration

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

Procedure: Synthesis in analogy to Example 8 and Example 19 starting from 3-[2-(4-amino-phenyl)-2-oxo-ethyl]-2-methyl-5,5-diphenyl-3,5-dihydro-imidazol-4-one and (2-methoxy-phenyl)-acetyl chloride to yield N-{4-[1-hydroxy-2-(2-methyl-5-oxo-4,4-diphenyl-4,5-dihydro-imidazol-1-yl)-ethyl]-phenyl}-2-(2-methoxy-phenyl)-acetamide. LC/MS at 254 nm; [M+H] 535: Rt=3.003 min.

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

Procedure: Synthesis in analogy to Example 8 and Example 19 starting from 3-[2-(4-amino-phenyl)-2-oxo-ethyl]-2-methyl-5,5-diphenyl-3,5-dihydro-imidazol-4-one and (2-methoxy-phenyl)-acetyl chloride to yield N-{4-[1-hydroxy-2-(2-methyl-5-oxo-4,4-diphenyl-4,5-dihydro-imidazol-1-yl)-ethyl]-phenyl}-2-(2-methoxy-phenyl)-acetamide. LC/MS at 254 nm; [M+H] 535: Rt=3.003 min.

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

Procedure: 8.80 g of a 50% aqueous sodium hydroxide solution, isopropylguanidine sulfate (16.52 g) and 100 ml of acetone, are stirred for 21/2 hrs at RT. The resulting mixture is treated with anhydrous sodium sulfate (6.0 g) and stirring continued for 1 hr. A solution of 2-methoxyphenylacetyl chloride (9.23 g) in 50 ml of acetone is added to the mixture dropwise and the mixture stirred overnight at RT. The resulting mixture is filtered and the filtrate diluted with 100 ml of saturated aqueous sodium bicarbonate. The acetone solvent is evaporated in vacuo. The residue is diluted with 100 ml H2O and extracted with two 100 ml portions of methylene chloride. The extract is dried with sodium sulfate, filtered and concentrated in vacuo. The concentrate is acidified with ethereal hydrochloric acid and the solvent evaporated in vacuo. The residue is stirred with 200 ml of diethyl ether, the solid collected and dried in air. The residual solid is recrystallized from acetone to afford 6.4 g of a white crystalline product, M.P. 154°-156° C. the mixture stirred overnight at RT The resulting mixture is filtered the filtrate diluted with 100 ml of saturated aqueous sodium bicarbonate The acetone solvent is evaporated in vacuo The residue is diluted with 100 ml H2O extracted with two 100 ml portions of methylene chloride The extract is dried with sodium sulfate filtered concentrated in vacuo the solvent evaporated in vacuo The residue is stirred with 200 ml of diethyl ether the solid collected dried in air The residual solid is recrystallized from acetone

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

Procedure: 8.80 g of a 50% aqueous sodium hydroxide solution, ethylguanidine sulfate (14.98 g) and 100 ml of acetone, are stirred for 21/2 hrs at RT. The resulting mixture is treated with anhydrous sodium sulfate (6.0 g) and stirring continued for 1 hr. A solution of 2-methoxyphenylacetyl chloride (9.23 g) in 50 ml of acetone is added to the mixture dropwise and stirring is continued overnight at RT. The reaction mixture is filtered, the filtrate diluted with 100 ml of saturated aqueous sodium bicarbonate and the acetone evaporated in vacuo. The residue is diluted with 100 ml H2O and extracted with two 100 ml portions of methylene chloride. The extract is dried with sodium sulfate, filtered and concentrated in vacuo. The concentrate is acidified with ethereal hydrochloric acid and the solvent evaporated in vacuo. After stirring the residue with 200 ml of diethyl ether, the solid is collected, washed with diethyl ether and dried in air. The residual solid is recrystallized from acetone affording a white solid, M.P. 127°-128° C. stirring is continued overnight at RT The reaction mixture is filtered the filtrate diluted with 100 ml of saturated aqueous sodium bicarbonate the acetone evaporated in vacuo The residue is diluted with 100 ml H2O extracted with two 100 ml portions of methylene chloride The extract is dried with sodium sulfate filtered concentrated in vacuo the solvent evaporated in vacuo After stirring the residue with 200 ml of diethyl ether the solid is collected washed with diethyl ether dried in air The residual solid is recrystallized from acetone affording a white solid, M.P. 127°-128° C.

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

Procedure: 8.80 g of a 50% aqueous sodium hydroxide solution, ethylguanidine sulfate (14.98 g) and 100 ml of acetone, are stirred for 21/2 hrs at RT. The resulting mixture is treated with anhydrous sodium sulfate (6.0 g) and stirring continued for 1 hr. A solution of 2-methoxyphenylacetyl chloride (9.23 g) in 50 ml of acetone is added to the mixture dropwise and stirring is continued overnight at RT. The reaction mixture is filtered, the filtrate diluted with 100 ml of saturated aqueous sodium bicarbonate and the acetone evaporated in vacuo. The residue is diluted with 100 ml H2O and extracted with two 100 ml portions of methylene chloride. The extract is dried with sodium sulfate, filtered and concentrated in vacuo. The concentrate is acidified with ethereal hydrochloric acid and the solvent evaporated in vacuo. After stirring the residue with 200 ml of diethyl ether, the solid is collected, washed with diethyl ether and dried in air. The residual solid is recrystallized from acetone affording a white solid, M.P. 127°-128° C. stirring is continued overnight at RT The reaction mixture is filtered the filtrate diluted with 100 ml of saturated aqueous sodium bicarbonate the acetone evaporated in vacuo The residue is diluted with 100 ml H2O extracted with two 100 ml portions of methylene chloride The extract is dried with sodium sulfate filtered concentrated in vacuo the solvent evaporated in vacuo After stirring the residue with 200 ml of diethyl ether the solid is collected washed with diethyl ether dried in air The residual solid is recrystallized from acetone affording a white solid, M.P. 127°-128° C.