Réaction #1344

Équation de réaction

sodium hydride

ethyl 4-chloroacetoacetate

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

→

title compound

Rendement 43.7%

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

Rendement 43.7%

Solvants

tetrahydrofuran

tetrahydrofuran

tetrahydrofuran

Conditions de réaction

Traitement

1. 1
   TempératureThe resulting mixture was cooled in an ice bath
2. 2
   Températurethen refluxed for 6 h
3. 3
   TempératureOn cooling to room temperature
4. 4
   Autrethe reaction mixture was quenched with 1N hydrochloric acid (20 mL) and volatile materials
5. 5
   Autrewere removed under reduced pressure
6. 6
   ExtractionThe aqueous phase was extracted with ethyl acetate (3×30 mL)
7. 7
   LavageThe combined organic fractions was washed with brine
8. 8
   Séchagedried (sodium sulfate)
9. 9
   Filtrationfiltered
10. 10
    Concentrationconcentrated in vacuo
11. 11
    AutreThe 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

Mode opératoire

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;

Source