ethyl 3-methyl-4-oxobutanoate

反応条件: temp:0.00; pressure:0.00; stir:

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

実験手順: In another example, an all-trans-13,14-dihydroretinol can be synthesized as follows. All reagents can be purchased from Sigma or Fluka and used without additional purification. Solvents can be dried under standard procedures prior to use. All operations with retinoids may be performed under dim red light unless otherwise specified. B-Ionone can be condensed with triethyl phosphonoacetate in anhydrous tetrahydrofuran in the presence of NaH to give ethyl trans-β-ionylideneacetate. This ester may then be reduced with LiAlH4 to alcohol and reacted overnight with triphenylphosphine hydrobromide to give Wittig salt. Ethyl 4-oxo-3-methylcrotonate can be hydrogenated in methanol with H2 using 10% palladium on carbon as a catalyst to yield ethyl 4-oxo-3-methylbutyrate, which may then be reacted with Wittig salt using t-BuOK as a base in anhydrous CH2Cl2 in the presence of 18-crown-6. The obtained mixture of ethyl 11-cis and all-trans-13,14-dihydroretinoates can be reduced with LiAlH4 to 13,14-dihydroretinols, and all-trans-isomer separated from 11-cis-dihydroretinol by flash chromatography of silica gel using 5% ethyl acetate in hexane. NMR data can be recorded on a Bruker 500-MHz spectrometer using CDCl3 as an internal standard. 1H NMR analysis of synthetic all-trans-13,14-dihydroretinol can yield: NMR (CDCl3, δ, ppm) 6.41 (dd, 1H, H-12, J=11.3, 14.75 Hz), 6.10-6.12 (m, 3H, H-7, H-8, H-10, J=15.7 Hz), 5.6 (dd, 1H, H-11, J=8.34, 14.95 Hz), 3.67 (m, 2H, CH2-15), 2.41 (m, 1H, H-13, J=6.7 Hz), 1.96 (m, 2H, CH2-14), 1.90 (s, 3H, CH3-9), 1.69 (s, 3H, CH3-5), 1.46 (m, 2H, CH2-2), 1.6 (m, 4H, CH2-3, CH2-4), 1.06 (d, 3H, CH3-13 J=6.7 Hz), 1.00 (s, 6H, 2×CH3-1).

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

実験手順: A solution of 53.18 g of 3A in 400 ml of dry methylene chloride was cooled to -78° C. Ozone was passed through the cold solution for 3.5 hours, air was passed through the solution for 10 minutes, then the solution was allowed to warm. At -50° C., 41.63 g of triethylamine was added drop-by-drop slowly. A strongly exothermic reaction occurred immediately, and the mixture was maintained at 5°-10° C. over the period of addition of the amine (30 minutes). The mixture then was stirred at room temperature for 2 hours, the solvents were evaporated under reduced pressure, and the residue was vacuum-chromatographed on silica gel, ether being used as eluent. The solution thus obtained was dried (MgSO4) and the solvent was evaporated to give ethyl 3-methyl-4-oxobutanoate (3B), as a slightly unstable pale yellow oil. to warm A strongly exothermic reaction the solvents were evaporated under reduced pressure the residue was vacuum-chromatographed on silica gel, ether being The solution thus obtained was dried (MgSO4) the solvent was evaporated

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

実験手順: In another example, an all-trans-13,14-dihydroretinol can be synthesized as follows. All reagents can be purchased from Sigma or Fluka and used without additional purification. Solvents can be dried under standard procedures prior to use. All operations with retinoids may be performed under dim red light unless otherwise specified. B-Ionone can be condensed with triethyl phosphonoacetate in anhydrous tetrahydrofuran in the presence of NaH to give ethyl trans-β-ionylideneacetate. This ester may then be reduced with LiAlH4 to alcohol and reacted overnight with triphenylphosphine hydrobromide to give Wittig salt. Ethyl 4-oxo-3-methylcrotonate can be hydrogenated in methanol with H2 using 10% palladium on carbon as a catalyst to yield ethyl 4-oxo-3-methylbutyrate, which may then be reacted with Wittig salt using t-BuOK as a base in anhydrous CH2Cl2 in the presence of 18-crown-6. The obtained mixture of ethyl 11-cis and all-trans-13,14-dihydroretinoates can be reduced with LiAlH4 to 13,14-dihydroretinols, and all-trans-isomer separated from 11-cis-dihydroretinol by flash chromatography of silica gel using 5% ethyl acetate in hexane. NMR data can be recorded on a Bruker 500-MHz spectrometer using CDCl3 as an internal standard. 1H NMR analysis of synthetic all-trans-13,14-dihydroretinol can yield: NMR (CDCl3, δ, ppm) 6.41 (dd, 1H, H-12, J=11.3, 14.75 Hz), 6.10-6.12 (m, 3H, H-7, H-8, H-10, J=15.7 Hz), 5.6 (dd, 1H, H-11, J=8.34, 14.95 Hz), 3.67 (m, 2H, CH2-15), 2.41 (m, 1H, H-13, J=6.7 Hz), 1.96 (m, 2H, CH2-14), 1.90 (s, 3H, CH3-9), 1.69 (s, 3H, CH3-5), 1.46 (m, 2H, CH2-2), 1.6 (m, 4H, CH2-3, CH2-4), 1.06 (d, 3H, CH3-13 J=6.7 Hz), 1.00 (s, 6H, 2×CH3-1).

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

実験手順: In another example, an all-trans-13,14-dihydroretinol can be synthesized as follows. All reagents can be purchased from Sigma or Fluka and used without additional purification. Solvents can be dried under standard procedures prior to use. All operations with retinoids may be performed under dim red light unless otherwise specified. B-Ionone can be condensed with triethyl phosphonoacetate in anhydrous tetrahydrofuran in the presence of NaH to give ethyl trans-β-ionylideneacetate. This ester may then be reduced with LiAlH4 to alcohol and reacted overnight with triphenylphosphine hydrobromide to give Wittig salt. Ethyl 4-oxo-3-methylcrotonate can be hydrogenated in methanol with H2 using 10% palladium on carbon as a catalyst to yield ethyl 4-oxo-3-methylbutyrate, which may then be reacted with Wittig salt using t-BuOK as a base in anhydrous CH2Cl2 in the presence of 18-crown-6. The obtained mixture of ethyl 11-cis and all-trans-13,14-dihydroretinoates can be reduced with LiAlH4 to 13,14-dihydroretinols, and all-trans-isomer separated from 11-cis-dihydroretinol by flash chromatography of silica gel using 5% ethyl acetate in hexane. NMR data can be recorded on a Bruker 500-MHz spectrometer using CDCl3 as an internal standard. 1H NMR analysis of synthetic all-trans-13,14-dihydroretinol can yield: NMR (CDCl3, δ, ppm) 6.41 (dd, 1H, H-12, J=11.3, 14.75 Hz), 6.10-6.12 (m, 3H, H-7, H-8, H-10, J=15.7 Hz), 5.6 (dd, 1H, H-11, J=8.34, 14.95 Hz), 3.67 (m, 2H, CH2-15), 2.41 (m, 1H, H-13, J=6.7 Hz), 1.96 (m, 2H, CH2-14), 1.90 (s, 3H, CH3-9), 1.69 (s, 3H, CH3-5), 1.46 (m, 2H, CH2-2), 1.6 (m, 4H, CH2-3, CH2-4), 1.06 (d, 3H, CH3-13 J=6.7 Hz), 1.00 (s, 6H, 2×CH3-1).

反応条件: temp:0.00; pressure:0.00; stir:

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

実験手順: In another example, an all-trans-13,14-dihydroretinol can be synthesized as follows. All reagents can be purchased from Sigma or Fluka and used without additional purification. Solvents can be dried under standard procedures prior to use. All operations with retinoids may be performed under dim red light unless otherwise specified. B-Ionone can be condensed with triethyl phosphonoacetate in anhydrous tetrahydrofuran in the presence of NaH to give ethyl trans-β-ionylideneacetate. This ester may then be reduced with LiAlH4 to alcohol and reacted overnight with triphenylphosphine hydrobromide to give Wittig salt. Ethyl 4-oxo-3-methylcrotonate can be hydrogenated in methanol with H2 using 10% palladium on carbon as a catalyst to yield ethyl 4-oxo-3-methylbutyrate, which may then be reacted with Wittig salt using t-BuOK as a base in anhydrous CH2Cl2 in the presence of 18-crown-6. The obtained mixture of ethyl 11-cis and all-trans-13,14-dihydroretinoates can be reduced with LiAlH4 to 13,14-dihydroretinols, and all-trans-isomer separated from 11-cis-dihydroretinol by flash chromatography of silica gel using 5% ethyl acetate in hexane. NMR data can be recorded on a Bruker 500-MHz spectrometer using CDCl3 as an internal standard. 1H NMR analysis of synthetic all-trans-13,14-dihydroretinol can yield: NMR (CDCl3, δ, ppm) 6.41 (dd, 1H, H-12, J=11.3, 14.75 Hz), 6.10-6.12 (m, 3H, H-7, H-8, H-10, J=15.7 Hz), 5.6 (dd, 1H, H-11, J=8.34, 14.95 Hz), 3.67 (m, 2H, CH2-15), 2.41 (m, 1H, H-13, J=6.7 Hz), 1.96 (m, 2H, CH2-14), 1.90 (s, 3H, CH3-9), 1.69 (s, 3H, CH3-5), 1.46 (m, 2H, CH2-2), 1.6 (m, 4H, CH2-3, CH2-4), 1.06 (d, 3H, CH3-13 J=6.7 Hz), 1.00 (s, 6H, 2×CH3-1).

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

実験手順: A solution of ethyl 3-(dimethoxymethyl)-crotonate (73 g) in ethyl acetate (200 ml) was hydrogenated at 50 psi for 3 h in the presence of 10% palladium on charcoal (7 g). The solution was filtered, evaporated, and the residual oil treated with 0.25 M hydrogen chloride in 75% aqueous methanol for 2 h. To the reaction mixture was added ethyl acetate (300 ml) and water (150 ml). The organic phase was successively washed with sat. sodium bicarbonate solution (3×150 ml), water (100 ml) and dried over magnesium sulfate. The solution was concentrated in vacuo and the residual oil purified by chromatography on silica gel eluting with ethyl acetate-hexane (1:9) to give ethyl 3-formylbutyrate (26.5 g, 48%). The solution was filtered evaporated the residual oil treated with 0.25 M hydrogen chloride in 75% aqueous methanol for 2 h To the reaction mixture was added ethyl acetate (300 ml) and water (150 ml) The organic phase was successively washed with sat. sodium bicarbonate solution (3×150 ml), water (100 ml) dried over magnesium sulfate The solution was concentrated in vacuo the residual oil purified by chromatography on silica gel eluting with ethyl acetate-hexane (1:9)

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

実験手順: A solution of 53.18 g of 3A in 400 ml of dry methylene chloride was cooled to -78° C. Ozone was passed through the cold solution for 3.5 hours, air was passed through the solution for 10 minutes, then the solution was allowed to warm. At -50° C., 41.63 g of triethylamine was added drop-by-drop slowly. A strongly exothermic reaction occurred immediately, and the mixture was maintained at 5°-10° C. over the period of addition of the amine (30 minutes). The mixture then was stirred at room temperature for 2 hours, the solvents were evaporated under reduced pressure, and the residue was vacuum-chromatographed on silica gel, ether being used as eluent. The solution thus obtained was dried (MgSO4) and the solvent was evaporated to give ethyl 3-methyl-4-oxobutanoate (3B), as a slightly unstable pale yellow oil. to warm A strongly exothermic reaction the solvents were evaporated under reduced pressure the residue was vacuum-chromatographed on silica gel, ether being The solution thus obtained was dried (MgSO4) the solvent was evaporated

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

実験手順: In another example, an all-trans-13,14-dihydroretinol can be synthesized as follows. All reagents can be purchased from Sigma or Fluka and used without additional purification. Solvents can be dried under standard procedures prior to use. All operations with retinoids may be performed under dim red light unless otherwise specified. B-Ionone can be condensed with triethyl phosphonoacetate in anhydrous tetrahydrofuran in the presence of NaH to give ethyl trans-β-ionylideneacetate. This ester may then be reduced with LiAlH4 to alcohol and reacted overnight with triphenylphosphine hydrobromide to give Wittig salt. Ethyl 4-oxo-3-methylcrotonate can be hydrogenated in methanol with H2 using 10% palladium on carbon as a catalyst to yield ethyl 4-oxo-3-methylbutyrate, which may then be reacted with Wittig salt using t-BuOK as a base in anhydrous CH2Cl2 in the presence of 18-crown-6. The obtained mixture of ethyl 11-cis and all-trans-13,14-dihydroretinoates can be reduced with LiAlH4 to 13,14-dihydroretinols, and all-trans-isomer separated from 11-cis-dihydroretinol by flash chromatography of silica gel using 5% ethyl acetate in hexane. NMR data can be recorded on a Bruker 500-MHz spectrometer using CDCl3 as an internal standard. 1H NMR analysis of synthetic all-trans-13,14-dihydroretinol can yield: NMR (CDCl3, δ, ppm) 6.41 (dd, 1H, H-12, J=11.3, 14.75 Hz), 6.10-6.12 (m, 3H, H-7, H-8, H-10, J=15.7 Hz), 5.6 (dd, 1H, H-11, J=8.34, 14.95 Hz), 3.67 (m, 2H, CH2-15), 2.41 (m, 1H, H-13, J=6.7 Hz), 1.96 (m, 2H, CH2-14), 1.90 (s, 3H, CH3-9), 1.69 (s, 3H, CH3-5), 1.46 (m, 2H, CH2-2), 1.6 (m, 4H, CH2-3, CH2-4), 1.06 (d, 3H, CH3-13 J=6.7 Hz), 1.00 (s, 6H, 2×CH3-1).