반응 #1344

반응 방정식

sodium hydride

ethyl 4-chloroacetoacetate

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

→

title compound

수율 43.7%

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

수율 43.7%

용매

tetrahydrofuran

tetrahydrofuran

tetrahydrofuran

반응 조건

후처리

1. 1
   온도The resulting mixture was cooled in an ice bath
2. 2
   온도then refluxed for 6 h
3. 3
   온도On cooling to room temperature
4. 4
   기타the reaction mixture was quenched with 1N hydrochloric acid (20 mL) and volatile materials
5. 5
   기타were removed under reduced pressure
6. 6
   추출The aqueous phase was extracted with ethyl acetate (3×30 mL)
7. 7
   세척The combined organic fractions was washed with brine
8. 8
   건조dried (sodium sulfate)
9. 9
   여과filtered
10. 10
    농축concentrated in vacuo
11. 11
    기타The 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

실험 절차

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;

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