4-ethyl-2-hydroxybenzaldehyde

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

実験手順: This compound was prepared in a manner analogous to that of Step (b) of Example 1, using 17.0 grams (0.113 mole) of 5-ethyl-2-formylphenol, 27.7 grams (0.116 mole) of 2-(1,1-dimethylethyldimethylsilyloxy)ethyl bromide, 19.2 grams (0.139 mole) of potassium carbonate, and a catalytic amount of 18-crown-6 in 200 mL of THF. The yield of the subject compound was 12.7 grams, following purification by column chromatography on silica gel. The NMR spectrum was consistent with the proposed structure. This compound was prepared in a manner analogous to that of Step (b) of Example 1 purification by column chromatography on silica gel

反応条件: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A stirred solution of 3.8 grams (0.026 mole) of 5-ethyl-2-formylphenol, 5.0 grams (0.026 mole) of 4-methylsulfonyloxymethyl-1,3-dioxane, and 7.0 grams (0.051 mole) of potassium carbonate in 150 mL of N,N-dimethylformamide was heated at 80° C. for about 18 hours. Analysis by thin layer chromatography (TLC) indicated the reaction was not complete. An additional 2.5 grams (0.013 mole) of 4-methylsulfonyloxymethyl-1,3-dioxane was added, and the reaction mixture was heated at 80° C. for an additional five hours. After this time the reaction mixture was poured into water and extracted with ethyl acetate. The extract was washed with aqueous 10% lithium chloride, dried with magnesium sulfate, and filtered. The filtrate was concentrated under reduced pressure to a residue. The residue was purified by column chromatography on silica gel, yielding 3.6 grams of the subject compound. The NMR spectrum was consistent with the proposed structure. extracted with ethyl acetate The extract was washed with aqueous 10% lithium chloride dried with magnesium sulfate filtered The filtrate was concentrated under reduced pressure to a residue The residue was purified by column chromatography on silica gel

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

実験手順: A stirred solution of 21.8 grams (0.15 mole) of 5-ethyl-2-formylphenol, 24.2 grams (0.15 mole) of methyl DL-2-bromopropanoate, and 30 grams (0.22 mole) of potassium carbonate in 300 mL of acetone was heated at reflux for about 18 hours. After this time, the reaction mixture was cooled and concentrated under reduced pressure to a residue. The residue was taken up in methylene chloride, washed first with water, and then with an aqueous 10% sodium hydroxide solution. The organic layer was dried with magnesium sulfate and filtered. The filtrate was concentrated under reduced pressure to a residue. The residue was subjected to column chromatography on silica gel, using a gradient elution starting with 50% methylene chloride in hexane and progressing to 100% methylene chloride. The product-containing fractions were combined and concentrated under reduced pressure, yielding 9.8 grams of methyl 2-(5-ethyl-2-formylphenoxy)propanoate. The NMR spectrum was consistent with the proposed structure. at reflux for about 18 hours After this time, the reaction mixture was cooled concentrated under reduced pressure to a residue washed first with water The organic layer was dried with magnesium sulfate filtered The filtrate was concentrated under reduced pressure to a residue a gradient elution concentrated under reduced pressure

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

実験手順: A stirred solution of 200 mL (0.20 mole) of 1.0M of ethylmagnesium bromide (in tetrahydrofuran) in 100 mL of tetrahydrofuran was cooled in an ice-bath and 25.0 grams (0.21 mole) of 3-ethylphenol was added dropwise. Upon completion of addition, the reaction mixture was allowed to warm to ambient temperature where it stirred for 30 minutes. After this time, 15.4 grams (0.51 mole) of paraformaldehyde, 36.7 grams (0.21 mole) of hexamethylphosphoramide, and 350 mL of toluene were added. Upon completion of addition, the reaction mixture was heated to 80° C. where it stirred for about 18 hours. The reaction mixture was then cooled and concentrated under reduced pressure to a residue. The residue was taken up in diethyl ether and 200 mL of an aqueous 10% hydrochloric acid solution was added. The aqueous layer was separated and extracted with diethyl ether. The extract was combined with the organic layer, and the combination was washed with water. The organic layer was dried with magnesium sulfate and filtered. The filtrate was concentrated under reduce pressure to a residue. The residue was subjected to column chromatography on silica gel, using 1:1 hexane and methylene chloride as the eluant. The product-containing fractions were combined and concentrated under reduced pressure, yielding 21.8 grams of 5-ethyl-2-formylphenol. The NMR spectrum was consistent with the proposed structure. Upon completion of addition Upon completion of addition the reaction mixture was heated to 80° C. where it stirred for about 18 hours The reaction mixture was then cooled concentrated under reduced pressure to a residue 200 mL of an aqueous 10% hydrochloric acid solution was added The aqueous layer was separated extracted with diethyl ether the combination was washed with water The organic layer was dried with magnesium sulfate filtered The filtrate was concentrated concentrated under reduced pressure

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

実験手順: Titanium(IV) chloride (100 mL, 100 mmol, 1M in CH2Cl2) followed by dichloromethyl methyl ether (7.47 mL, 82.5 mmol) was added to a cooled 0° C. solution of 3-ethylphenol (6.11 g, 50 mmol). The reaction mixture was stirred for 45 mins. The mixture was poured into ice and extracted with EtOAc. The organic layers were washed with brine, dried over Na2SO4 and concentrated to a bright pink oil. Purification by flash column chromatography (0% to 10% EtOAc in hexanes) gave 4-ethyl-2-hydroxy-benzaldehyde (4.9 g, 65%) followed by 2-ethyl-4-hydroxy-benzaldehyde (1.32 g, 18%). A: The mixture was poured into ice extracted with EtOAc The organic layers were washed with brine dried over Na2SO4 concentrated to a bright pink oil Purification by flash column chromatography (0% to 10% EtOAc in hexanes)

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

実験手順: By the method of Example 1, Step F, 32.33 grams (0.215 mole) of 4-ethylsalicylaldehyde and 35.9 grams (0.215 mole) of methyl 2-bromopropionate was reacted in the presence of 35.7 grams (0.258 mole) of potassium carbonate in 50 mL of tetrahydrofuran, yielding 49.16 grams of methyl 2-(2-formyl-4-ethylphenoxy)propionate. The NMR spectrum was consistent with the proposed spectrum.

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

実験手順: This compound was prepared in a manner analogous to that of Step (b) of Example 1, using 17.0 grams (0.113 mole) of 5-ethyl-2-formylphenol, 27.7 grams (0.116 mole) of 2-(1,1-dimethylethyldimethylsilyloxy)ethyl bromide, 19.2 grams (0.139 mole) of potassium carbonate, and a catalytic amount of 18-crown-6 in 200 mL of THF. The yield of the subject compound was 12.7 grams, following purification by column chromatography on silica gel. The NMR spectrum was consistent with the proposed structure. This compound was prepared in a manner analogous to that of Step (b) of Example 1 purification by column chromatography on silica gel

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

実験手順: This compound was prepared in a manner analogous to that of Step (b) of Example 1, using 17.0 grams (0.113 mole) of 5-ethyl-2-formylphenol, 27.7 grams (0.116 mole) of 2-(1,1-dimethylethyldimethylsilyloxy)ethyl bromide, 19.2 grams (0.139 mole) of potassium carbonate, and a catalytic amount of 18-crown-6 in 200 mL of THF. The yield of the subject compound was 12.7 grams, following purification by column chromatography on silica gel. The NMR spectrum was consistent with the proposed structure. This compound was prepared in a manner analogous to that of Step (b) of Example 1 purification by column chromatography on silica gel

反応条件: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A stirred solution of 3.8 grams (0.026 mole) of 5-ethyl-2-formylphenol, 5.0 grams (0.026 mole) of 4-methylsulfonyloxymethyl-1,3-dioxane, and 7.0 grams (0.051 mole) of potassium carbonate in 150 mL of N,N-dimethylformamide was heated at 80° C. for about 18 hours. Analysis by thin layer chromatography (TLC) indicated the reaction was not complete. An additional 2.5 grams (0.013 mole) of 4-methylsulfonyloxymethyl-1,3-dioxane was added, and the reaction mixture was heated at 80° C. for an additional five hours. After this time the reaction mixture was poured into water and extracted with ethyl acetate. The extract was washed with aqueous 10% lithium chloride, dried with magnesium sulfate, and filtered. The filtrate was concentrated under reduced pressure to a residue. The residue was purified by column chromatography on silica gel, yielding 3.6 grams of the subject compound. The NMR spectrum was consistent with the proposed structure. extracted with ethyl acetate The extract was washed with aqueous 10% lithium chloride dried with magnesium sulfate filtered The filtrate was concentrated under reduced pressure to a residue The residue was purified by column chromatography on silica gel

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

実験手順: A stirred solution of 21.8 grams (0.15 mole) of 5-ethyl-2-formylphenol, 24.2 grams (0.15 mole) of methyl DL-2-bromopropanoate, and 30 grams (0.22 mole) of potassium carbonate in 300 mL of acetone was heated at reflux for about 18 hours. After this time, the reaction mixture was cooled and concentrated under reduced pressure to a residue. The residue was taken up in methylene chloride, washed first with water, and then with an aqueous 10% sodium hydroxide solution. The organic layer was dried with magnesium sulfate and filtered. The filtrate was concentrated under reduced pressure to a residue. The residue was subjected to column chromatography on silica gel, using a gradient elution starting with 50% methylene chloride in hexane and progressing to 100% methylene chloride. The product-containing fractions were combined and concentrated under reduced pressure, yielding 9.8 grams of methyl 2-(5-ethyl-2-formylphenoxy)propanoate. The NMR spectrum was consistent with the proposed structure. at reflux for about 18 hours After this time, the reaction mixture was cooled concentrated under reduced pressure to a residue washed first with water The organic layer was dried with magnesium sulfate filtered The filtrate was concentrated under reduced pressure to a residue a gradient elution concentrated under reduced pressure

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

実験手順: A stirred solution of 200 mL (0.20 mole) of 1.0M of ethylmagnesium bromide (in tetrahydrofuran) in 100 mL of tetrahydrofuran was cooled in an ice-bath and 25.0 grams (0.21 mole) of 3-ethylphenol was added dropwise. Upon completion of addition, the reaction mixture was allowed to warm to ambient temperature where it stirred for 30 minutes. After this time, 15.4 grams (0.51 mole) of paraformaldehyde, 36.7 grams (0.21 mole) of hexamethylphosphoramide, and 350 mL of toluene were added. Upon completion of addition, the reaction mixture was heated to 80° C. where it stirred for about 18 hours. The reaction mixture was then cooled and concentrated under reduced pressure to a residue. The residue was taken up in diethyl ether and 200 mL of an aqueous 10% hydrochloric acid solution was added. The aqueous layer was separated and extracted with diethyl ether. The extract was combined with the organic layer, and the combination was washed with water. The organic layer was dried with magnesium sulfate and filtered. The filtrate was concentrated under reduce pressure to a residue. The residue was subjected to column chromatography on silica gel, using 1:1 hexane and methylene chloride as the eluant. The product-containing fractions were combined and concentrated under reduced pressure, yielding 21.8 grams of 5-ethyl-2-formylphenol. The NMR spectrum was consistent with the proposed structure. Upon completion of addition Upon completion of addition the reaction mixture was heated to 80° C. where it stirred for about 18 hours The reaction mixture was then cooled concentrated under reduced pressure to a residue 200 mL of an aqueous 10% hydrochloric acid solution was added The aqueous layer was separated extracted with diethyl ether the combination was washed with water The organic layer was dried with magnesium sulfate filtered The filtrate was concentrated concentrated under reduced pressure

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

実験手順: A stirred solution of 200 mL (0.20 mole) of 1.0M of ethylmagnesium bromide (in tetrahydrofuran) in 100 mL of tetrahydrofuran was cooled in an ice-bath and 25.0 grams (0.21 mole) of 3-ethylphenol was added dropwise. Upon completion of addition, the reaction mixture was allowed to warm to ambient temperature where it stirred for 30 minutes. After this time, 15.4 grams (0.51 mole) of paraformaldehyde, 36.7 grams (0.21 mole) of hexamethylphosphoramide, and 350 mL of toluene were added. Upon completion of addition, the reaction mixture was heated to 80° C. where it stirred for about 18 hours. The reaction mixture was then cooled and concentrated under reduced pressure to a residue. The residue was taken up in diethyl ether and 200 mL of an aqueous 10% hydrochloric acid solution was added. The aqueous layer was separated and extracted with diethyl ether. The extract was combined with the organic layer, and the combination was washed with water. The organic layer was dried with magnesium sulfate and filtered. The filtrate was concentrated under reduce pressure to a residue. The residue was subjected to column chromatography on silica gel, using 1:1 hexane and methylene chloride as the eluant. The product-containing fractions were combined and concentrated under reduced pressure, yielding 21.8 grams of 5-ethyl-2-formylphenol. The NMR spectrum was consistent with the proposed structure. Upon completion of addition Upon completion of addition the reaction mixture was heated to 80° C. where it stirred for about 18 hours The reaction mixture was then cooled concentrated under reduced pressure to a residue 200 mL of an aqueous 10% hydrochloric acid solution was added The aqueous layer was separated extracted with diethyl ether the combination was washed with water The organic layer was dried with magnesium sulfate filtered The filtrate was concentrated concentrated under reduced pressure