Reaktion #1344

Reaktionsgleichung

sodium hydride

ethyl 4-chloroacetoacetate

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

→

title compound

Ausbeute 43.7%

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

Ausbeute 43.7%

Lösungsmittel

tetrahydrofuran

tetrahydrofuran

tetrahydrofuran

Reaktionsbedingungen

Aufarbeitung

1. 1
   TemperaturThe resulting mixture was cooled in an ice bath
2. 2
   Temperaturthen refluxed for 6 h
3. 3
   TemperaturOn cooling to room temperature
4. 4
   Sonstigethe reaction mixture was quenched with 1N hydrochloric acid (20 mL) and volatile materials
5. 5
   Sonstigewere removed under reduced pressure
6. 6
   ExtraktionThe aqueous phase was extracted with ethyl acetate (3×30 mL)
7. 7
   WaschenThe combined organic fractions was washed with brine
8. 8
   Trocknendried (sodium sulfate)
9. 9
   Filtrationfiltered
10. 10
    Einengenconcentrated in vacuo
11. 11
    SonstigeThe 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

Vorschrift

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;

Quelle