反応 #317892

反応方程式

sodium hydride

(S)-(+)-2-pyrrolidinemethanol

3-chlorothiophene-2-carboxylic acid

1,1′-carbonyldiimidazole

→

title compound

収率 11.3%

(S)-2,3,10,10a-tetrahydro-1H,5H-pyrrolo[2,1-c]thieno[2,3-f][1,4]oxazepine-5-one

収率 11.3%

溶媒

water

dimethylformamide

反応条件

後処理

1. 1
   workup.ADDITIONwas carefully added
2. 2
   温度the mixture was heated slowly to 150° C. with the progress of the reaction
3. 3
   抽出extracted with ethyl acetate
4. 4
   洗浄the organic layer washed with water
5. 5
   乾燥then dried (Na2SO4)
6. 6
   その他evaporated
7. 7
   その他to give the crude product
8. 8
   その他Purification by flash chromatography
9. 9
   洗浄eluting with 0-10% (v/v) methanol in dichloromethane
10. 10
    その他followed by crystallisation from ethyl acetate-petroleum ether (40-60)

実験手順

To a solution of 3-chlorothiophene-2-carboxylic acid (0.5 g; 6.325 mmol) in dimethylformamide (5 ml) was added 1,1′-carbonyldiimidazole (1.07 g; 6.64 mmol) and the solution stirred at room temperature for 1 h, followed by the addition of (S)-(+)-2-pyrrolidinemethanol (0.655 ml; 6.64 mmol). The reaction was stirred at room temperature overnight whereupon 60% sodium hydride in mineral oil (0.507 g; 12.7 mmol) was carefully added and the mixture was heated slowly to 150° C. with the progress of the reaction being monitored by thin layer chromatography. The reaction was cautiously diluted with water and extracted with ethyl acetate and the organic layer washed with water then dried (Na2SO4) and evaporated to give the crude product. Purification by flash chromatography eluting with 0-10% (v/v) methanol in dichloromethane followed by crystallisation from ethyl acetate-petroleum ether (40-60) afforded the title compound (0.15 g). M.p.: 167-167.5° C.; EIMS: m/z=222.2 [M+H]+

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