تفاعل #1344

معادلة التفاعل

sodium hydride

ethyl 4-chloroacetoacetate

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

→

title compound

المردود 43.7%

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

المردود 43.7%

المذيبات

tetrahydrofuran

tetrahydrofuran

tetrahydrofuran

ظروف التفاعل

المعالجة

1. 1
   درجة الحرارةThe resulting mixture was cooled in an ice bath
2. 2
   درجة الحرارةthen refluxed for 6 h
3. 3
   درجة الحرارةOn cooling to room temperature
4. 4
   أخرىthe reaction mixture was quenched with 1N hydrochloric acid (20 mL) and volatile materials
5. 5
   أخرىwere removed under reduced pressure
6. 6
   استخلاصThe aqueous phase was extracted with ethyl acetate (3×30 mL)
7. 7
   غسيلThe combined organic fractions was washed with brine
8. 8
   تجفيفdried (sodium sulfate)
9. 9
   ترشيحfiltered
10. 10
    تركيزconcentrated in vacuo
11. 11
    أخرىThe 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

الإجراء التجريبي

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;

المصدر