1-(2,3-dichloro-4-hydroxyphenyl)butan-1-one

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

Procedure: A mixture of 2,3-dichloro-4-butyrylphenol (15 g, 0.064 mole), acetone (140 ml) and sodium hydroxide (14.5 g, 0.36 mole) was stirred and heated to reflux. Chloroform (12 g, 0.1 mole) was added to the mixture dropwise over a period of 15 minutes. Refluxing was continued for 3 hours and the acetone was evaporated in vacuo. The residue was treated with ice water containing hydrochloric acid. The product was extracted with ether. The ether extract was washed with water, then with brine and finally dried over MgSO4. The ether was evaporated in vacuo and the residue chromatographed on a column containing silica gel (320 g) and eluted with methylene chloride/tetrahydrofuran/acetic acid 50/1/1. The appropriate fractions were combined and evaporated in vacuo to give 10 g of 2-(2,3-dichloro-4-butyrylphenoxy)-2-methylpropionic acid which was identified by NMR and the purity confirmed by thin layer chromatography. heated to reflux Refluxing the acetone was evaporated in vacuo The residue was treated with ice water containing hydrochloric acid The product was extracted with ether The ether extract was washed with water with brine and finally dried over MgSO4 The ether was evaporated in vacuo the residue chromatographed on a column containing silica gel (320 g) eluted with methylene chloride/tetrahydrofuran/acetic acid 50/1/1 evaporated in vacuo

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

Procedure: A mixture of 2,3-dichloro-4-butyrylphenol (15 g, 0.064 mole), acetone (140 ml) and sodium hydroxide (14.5 g, 0.36 mole) was stirred and heated to reflux. Chloroform (12 g, 0.1 mole) was added to the mixture dropwise over a period of 15 minutes. Refluxing was continued for 3 hours and the acetone was evaporated in vacuo. The residue was treated with ice water containing hydrochloric acid. The product was extracted with ether. The ether extract was washed with water, then with brine and finally dried over MgSO4. The ether was evaporated in vacuo and the residue chromatographed on a column containing silica gel (320 g) and eluted with methylene chloride/tetrahydrofuran/acetic acid 50/1/1. The appropriate fractions were combined and evaporated in vacuo to give 10 g of 2-(2,3-dichloro-4-butyrylphenoxy)-2-methylpropionic acid which was identified by NMR and the purity confirmed by thin layer chromatography. heated to reflux Refluxing the acetone was evaporated in vacuo The residue was treated with ice water containing hydrochloric acid The product was extracted with ether The ether extract was washed with water with brine and finally dried over MgSO4 The ether was evaporated in vacuo the residue chromatographed on a column containing silica gel (320 g) eluted with methylene chloride/tetrahydrofuran/acetic acid 50/1/1 evaporated in vacuo

Conditions: temp:65.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 2,3-dichloro-4-butyrylphenol (7 g, 0.03 mole), ethyl 1-bromocyclobutanecarboxylate (10.23 g, 0.049 mole) and potassium carbonate (7.5 g, 0.054 mole) in N,N-dimethylformamide (60 ml) was stirred and heated at 65° C. for 18 hours. The reaction mixture was poured into ice water and the resulting mixture was extracted with ether. The ether extract was washed with a 1% sodium hydroxide solution, then with water and finally dried over MgSO4. The ether was evaporated in vacuo and the residue treated with acetic acid (60 ml) and 5% hydrochloric acid (15 ml). The mixture was stirred and refluxed overnight. The solvents were evaporated in vacuo. The residue was chromatographed over a column containing silica gel (140 g) using methylene chloride/tetrahydrofuran/acetic acid 50/1/1 as the eluent. The pertinent fractions were united, treated with toluene and evaporated in vacuo to obtain 1-(2,3-dichloro-4-butyrylphenoxy)cyclobutane-1-carboxylic acid as a liquid whose identity was confirmed by NMR and purity by thin layer chromatography. the resulting mixture was extracted with ether The ether extract was washed with a 1% sodium hydroxide solution with water and finally dried over MgSO4 The ether was evaporated in vacuo the residue treated with acetic acid (60 ml) and 5% hydrochloric acid (15 ml) The mixture was stirred refluxed overnight The solvents were evaporated in vacuo The residue was chromatographed over a column containing silica gel (140 g) treated with toluene evaporated in vacuo

Conditions: temp:65.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 2,3-dichloro-4-butyrylphenol (7 g, 0.03 mole), ethyl 1-bromocyclobutanecarboxylate (10.23 g, 0.049 mole) and potassium carbonate (7.5 g, 0.054 mole) in N,N-dimethylformamide (60 ml) was stirred and heated at 65° C. for 18 hours. The reaction mixture was poured into ice water and the resulting mixture was extracted with ether. The ether extract was washed with a 1% sodium hydroxide solution, then with water and finally dried over MgSO4. The ether was evaporated in vacuo and the residue treated with acetic acid (60 ml) and 5% hydrochloric acid (15 ml). The mixture was stirred and refluxed overnight. The solvents were evaporated in vacuo. The residue was chromatographed over a column containing silica gel (140 g) using methylene chloride/tetrahydrofuran/acetic acid 50/1/1 as the eluent. The pertinent fractions were united, treated with toluene and evaporated in vacuo to obtain 1-(2,3-dichloro-4-butyrylphenoxy)cyclobutane-1-carboxylic acid as a liquid whose identity was confirmed by NMR and purity by thin layer chromatography. the resulting mixture was extracted with ether The ether extract was washed with a 1% sodium hydroxide solution with water and finally dried over MgSO4 The ether was evaporated in vacuo the residue treated with acetic acid (60 ml) and 5% hydrochloric acid (15 ml) The mixture was stirred refluxed overnight The solvents were evaporated in vacuo The residue was chromatographed over a column containing silica gel (140 g) treated with toluene evaporated in vacuo

Conditions: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 2,3-dichloro-4-butyrylphenol (7 g, 0.03 mole), potassium carbonate (7.5 g, 0.054 mole) and ethyl 5-bromovalerate (9.5 g, 0.045 mole) in N,N-dimethylformamide (60 ml) were stirred and heated at 60° C. for 3 hours. The mixture was treated with 10 normal sodium hydroxide (12 ml) and water (50 ml), then stirred and heated on a steam bath for 2.5 hours. The solution was poured into ice water containing hydrochloric acid. The solid that separated was removed by filtration, washed with water and dried. The product (9.8 g) was recrystallized from butyl chloride to give 5-(2,3-dichloro-4-butyrylphenoxy)valeric acid, m.p. 102°-103° C. stirred heated on a steam bath for 2.5 hours The solid that separated was removed by filtration washed with water dried The product (9.8 g) was recrystallized from butyl chloride

Conditions: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 2,3-dichloro-4-butyrylphenol (7 g, 0.03 mole), potassium carbonate (7.5 g, 0.054 mole) and ethyl 5-bromovalerate (9.5 g, 0.045 mole) in N,N-dimethylformamide (60 ml) were stirred and heated at 60° C. for 3 hours. The mixture was treated with 10 normal sodium hydroxide (12 ml) and water (50 ml), then stirred and heated on a steam bath for 2.5 hours. The solution was poured into ice water containing hydrochloric acid. The solid that separated was removed by filtration, washed with water and dried. The product (9.8 g) was recrystallized from butyl chloride to give 5-(2,3-dichloro-4-butyrylphenoxy)valeric acid, m.p. 102°-103° C. stirred heated on a steam bath for 2.5 hours The solid that separated was removed by filtration washed with water dried The product (9.8 g) was recrystallized from butyl chloride

Conditions: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 2,3-dichloro-4-butyrylphenol (69.9 g, 0.30 mole), potassium carbonate (75 g, 0.54 mole) and ethyl 4-bromobutyrate (87.8 g, 0.45 mole) in N,N-dimethylformamide (900 ml of sieve-dried material) were stirred and heated at 55°-60° C. for 16.5 hours. The mixture was then treated with 10 normal sodium hydroxide solution (120 ml) and water (600 ml) and stirring and heating at 100° C. maintained for 2 hours. The solution was cooled and poured into ice water (4 liters) containing concentrated hydrochloric acid (250 ml). The solid that separated was removed by filtration, washed with water and dried. The product (88 g) was recrystallized from butyl chloride (500 ml) to give 78.6 g of 4-(2,3-dichloro-4-butyrylphenoxy)butyric acid, m.p. 111°-113° C. heated at 55°-60° C. for 16.5 hours stirring maintained for 2 hours The solution was cooled The solid that separated was removed by filtration washed with water dried The product (88 g) was recrystallized from butyl chloride (500 ml)

Conditions: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 2,3-dichloro-4-butyrylphenol (69.9 g, 0.30 mole), potassium carbonate (75 g, 0.54 mole) and ethyl 4-bromobutyrate (87.8 g, 0.45 mole) in N,N-dimethylformamide (900 ml of sieve-dried material) were stirred and heated at 55°-60° C. for 16.5 hours. The mixture was then treated with 10 normal sodium hydroxide solution (120 ml) and water (600 ml) and stirring and heating at 100° C. maintained for 2 hours. The solution was cooled and poured into ice water (4 liters) containing concentrated hydrochloric acid (250 ml). The solid that separated was removed by filtration, washed with water and dried. The product (88 g) was recrystallized from butyl chloride (500 ml) to give 78.6 g of 4-(2,3-dichloro-4-butyrylphenoxy)butyric acid, m.p. 111°-113° C. heated at 55°-60° C. for 16.5 hours stirring maintained for 2 hours The solution was cooled The solid that separated was removed by filtration washed with water dried The product (88 g) was recrystallized from butyl chloride (500 ml)

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

Procedure: A mixture of 2,3-dichloro-4-butyrylphenol (15 g, 0.064 mole), acetone (140 ml) and sodium hydroxide (14.5 g, 0.36 mole) was stirred and heated to reflux. Chloroform (12 g, 0.1 mole) was added to the mixture dropwise over a period of 15 minutes. Refluxing was continued for 3 hours and the acetone was evaporated in vacuo. The residue was treated with ice water containing hydrochloric acid. The produce was extracted with ether. The ether extract was washed with water, then with brine and finally dried over MgSO4. The ether was evaporated in vacuo and the residue chromatographed on a column containing silica gel (320 g) and eluted with methylene chloride/tetrahydrofuran/acetic acid 50/1/1. The appropriate fractions were combined and evaporated in vacuo to give 10 g of 2-(2,3-dichloro-4-butyrylphenoxy)-2-methylpropionic acid which was identified by NMR and the purity confirmed by thin layer chromatography. heated to reflux Refluxing the acetone was evaporated in vacuo The residue was treated with ice water containing hydrochloric acid The produce was extracted with ether The ether extract was washed with water with brine and finally dried over MgSO4 The ether was evaporated in vacuo the residue chromatographed on a column containing silica gel (320 g) eluted with methylene chloride/tetrahydrofuran/acetic acid 50/1/1 evaporated in vacuo

Conditions: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 2,3-dichloro-4-butyrylphenol (7 g, 0.03 mole), potassium carbonate (7.5 g, 0.054 mole) and ethyl 5-bromovalerate (9.5 g, 0.045 mole) in N,N-dimethylformamide (60 ml) were stirred and heated at 60° C. for 3 hours. The mixture was treated with 10 normal sodium hydroxide (12 ml) and water (50 ml), then stirred and heated on a steam bath for 2.5 hours. The solution was poured into ice water containing hydrochloric acid. The solid that separated was removed by filtration, washed with water and dried. The product (9.8 g) was recrystallized from butyl chloride to give 5-(2,3-dichloro-4-butyrylphenoxy)valeric acid, m.p. 102°-103° C. stirred heated on a steam bath for 2.5 hours The solid that separated was removed by filtration washed with water dried The product (9.8 g) was recrystallized from butyl chloride

Conditions: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 2,3-dichloro-4-butyrylphenol (69.9 g, 0.30 mole), potassium carbonate (75 g, 0.54 mole) and ethyl 4-bromobutyrate (87.8 g, 0.45 mole) in N,N-dimethylformamide (900 ml of sieve-dried material) were stirred and heated at 55°-60° C. for 16.5 hours. The mixture was then treated with 10 normal sodium hydroxide solution (120 ml) and water (600 ml) and stirring and heating at 100° C. maintained for 2 hours. The solution was cooled and poured into ice water (4 liters) containing concentrated hydrochloric acid (250 ml). The solid that separated was removed by filtration, washed with water and dried. The product (88 g) was recrystallized from butyl chloride (500 ml) to give 78.6 g of 4-(2,3-dichloro-4-butyrylphenoxy)butyric acid, m.p. 111°-113° C. heated at 55°-60° C. for 16.5 hours stirring maintained for 2 hours The solution was cooled The solid that separated was removed by filtration washed with water dried The product (88 g) was recrystallized from butyl chloride (500 ml)

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

Procedure: A mixture of 2,3-dichloro-4-butyrylphenol (15 g, 0.064 mole), acetone (140 ml) and sodium hydroxide (14.5 g, 0.36 mole) was stirred and heated to reflux. Chloroform (12 g, 0.1 mole) was added to the mixture dropwise over a period of 15 minutes. Refluxing was continued for 3 hours and the acetone was evaporated in vacuo. The residue was treated with ice water containing hydrochloric acid. The product was extracted with ether. The ether extract was washed with water, then with brine and finally dried over MgSO4. The ether was evaporated in vacuo and the residue chromatographed on a column containing silica gel (320 g) and eluted with methylene chloride/tetrahydrofuran/acetic acid 50/1/1. The appropriate fractions were combined and evaporated in vacuo to give 10 g of 2-(2,3-dichloro-4-butyrylphenoxy)-2-methylpropionic acid which was identified by NMR and the purity confirmed by thin layer chromatography. heated to reflux Refluxing the acetone was evaporated in vacuo The residue was treated with ice water containing hydrochloric acid The product was extracted with ether The ether extract was washed with water with brine and finally dried over MgSO4 The ether was evaporated in vacuo the residue chromatographed on a column containing silica gel (320 g) eluted with methylene chloride/tetrahydrofuran/acetic acid 50/1/1 evaporated in vacuo