反応 #1345

反応方程式

ethyl 4-chloroacetoacetate

2,2-dimethyl-[1,3]dioxolane-4-methanol

sodium hydride

→

title compound

収率 50.1%

4-(2,2-Dimethyl-[1,3]dioxolan-4-ylmethoxy)-3-oxo-butyric acid ethyl ester

収率 50.1%

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
   その他The reaction mixture was then quenched with water (100 mL) and tetrahydrofuran
3. 3
   その他was removed under reduced pressure
4. 4
   抽出The aqueous phase was extracted with ethyl acetate (3×250 mL)
5. 5
   乾燥The combined organic fractions was dried (sodium sulfate)
6. 6
   ろ過filtered
7. 7
   濃縮concentrated in vacuo
8. 8
   その他The residue was purified by flash chromatography on silica gel (grade 9385, Merck, 230-400 mesh, 60 Å)
9. 9
   workup.ADDITIONa mixture of hexane and ethyl acetate (9:1 and 8:2

実験手順

To a suspension of sodium hydride (55 g, 60% dispersion in oil) in tetrahydrofuran (1L) under a nitrogen atmosphere was added a solution of 2,2-dimethyl-[1,3]dioxolane-4-methanol (XV, 102.4 g) in tetrahydrofuran (250 mL) over 15 min at room temperature. The resulting mixture was cooled in an ice bath and a solution of ethyl 4-chloroacetoacetate (VIII, 102.9 g) in tetrahydrofuran (250 mL) was added dropwise over a period of 1 h. The reaction mixture was stirred at room temperature for 20 h. The reaction mixture was then quenched with water (100 mL) and tetrahydrofuran was removed under reduced pressure. The aqueous phase was extracted with ethyl acetate (3×250 mL). The combined organic fractions was 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 (9:1 and 8:2; 2L each) as eluent, thereby affording the title compound (XVI, 81.6 g). IR (neat, cm-1): 1736. (Alker, D. J. Med. Chem. 1991, 34, 19).

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