反応 #1344

反応方程式

sodium hydride

ethyl 4-chloroacetoacetate

2,2-dimethyl-[1,3]dioxolane-4,5-dimethanol

→

title compound

収率 43.7%

4-[5-(3-Ethoxycarbonyl-2-oxo-propoxymethyl)-2,2-dimethyl-[1,3]dioxolan-4-ylmethoxy]-3-oxo-butyric acid ethyl ester

収率 43.7%

溶媒

tetrahydrofuran

tetrahydrofuran

tetrahydrofuran

反応条件

後処理

1. 1
   温度The resulting mixture was cooled in an ice bath
2. 2
   温度then refluxed for 6 h
3. 3
   温度On cooling to room temperature
4. 4
   その他the reaction mixture was quenched with 1N hydrochloric acid (20 mL) and volatile materials
5. 5
   その他were removed under reduced pressure
6. 6
   抽出The aqueous phase was extracted with ethyl acetate (3×30 mL)
7. 7
   洗浄The combined organic fractions was washed with brine
8. 8
   乾燥dried (sodium sulfate)
9. 9
   ろ過filtered
10. 10
    濃縮concentrated in vacuo
11. 11
    その他The residue was purified by flash chromatography on silica gel (grade 9385, Merck, 230-400 mesh, 60 Å)
12. 12
    workup.ADDITIONa mixture of hexane and ethyl acetate (8:2, 7:3 and 6:4; 500 mL each) as eluent

実験手順

To a suspension of sodium hydride (4.0 g, 60% dispersion in oil) in tetrahydrofuran (150 mL) under a nitrogen atmosphere was added a solution of 2,2-dimethyl-[1,3]dioxolane-4,5-dimethanol (VII, 4.05 g) in tetrahydrofuran (25 mL) over 2 min at room temperature, followed by solid tetrabutylammonium hydrogen sulfate (0.4 g). The resulting mixture was cooled in an ice bath and a solution of ethyl 4-chloroacetoacetate (VIII, 8.1 g) in tetrahydrofuran (25 mL) was added dropwise over a period of 15 min. The reaction mixture was warmed to room temperature over 1 h then refluxed for 6 h. On cooling to room temperature, the reaction mixture was quenched with 1N hydrochloric acid (20 mL) and volatile materials were removed under reduced pressure. The aqueous phase was extracted with ethyl acetate (3×30 mL). The combined organic fractions was washed with brine, dried (sodium sulfate), filtered and concentrated in vacuo. The residue was purified by flash chromatography on silica gel (grade 9385, Merck, 230-400 mesh, 60 Å) using a mixture of hexane and ethyl acetate (8:2, 7:3 and 6:4; 500 mL each) as eluent, thereby affording the title compound (IX 4.5 g) as an oil and the mono O-alkylated compound, 4-(2-chlorophenyl)-2-(5-hydroxymethyl-2,2-dimethyl-[1,3]dioxolan-4-ylmethoxy-methyl-1,4-dihydro-6-methyl-3,5-pyridinedicarboxylic acid 3-ethyl 5-methyl ester (X, 1.95 g). Compound IX. IR (neat, cm-1): 1723, 1636; MS (CI): 436 (100%, [M+NH4 ]+). Compound X. IR (neat, cm-1): 3455, 1734;

出典