反応 #409412

反応方程式

3,3,3-trifluoro-2-hydroxy-2-methylpropanoic acid

thionyl chloride

9-amino-4,10-dihydrothieno[3,2-c][1]benzothiepin-10-one

→

9-(3,3,3-trifluoro-2-hydroxy-2-methylpropanoylamino)-4,10-dihydrothieno[3,2-c][1]benzothiepin-10-one

収率 63.0%

溶媒

dimethylacetamide

反応条件

後処理

1. 1
   workup.ADDITIONwas added
2. 2
   workup.STIRRINGthe mixture was stirred overnight at room temperature
3. 3
   濃縮After the reaction mixture was concentrated under reduced pressure
4. 4
   workup.DISSOLUTIONthe obtained oily residue was dissolved in ethyl acetate (50 ml)
5. 5
   洗浄The organic layer was washed successively with a 5% aqueous solution of sodium hydrogen carbonate
6. 6
   乾燥a saturated aqueous solution of sodium chloride, and then dried over anhydrous magnesium sulfate
7. 7
   ろ過After the drying agent was filtered off
8. 8
   濃縮the organic layer was concentrated under reduced pressure
9. 9
   その他The obtained oily residue was purified by silica gel column chromatography (hexane/ethyl acetate=5/1)

実験手順

In dimethylacetamide (10 ml) was dissolved 3,3,3-trifluoro-2-hydroxy-2-methylpropanoic acid (0.79 g, 5.0 mmol), and thionyl chloride (0.36 ml, 5.0 mmol) was added thereto at −15  C., followed by stirring at −15 to −5° C. for one hour. To the resulting mixture was added 9-amino-4,10-dihydrothieno[3,2-c][1]benzothiepin-10-one obtained in Reference Example 5 (0.62 g, 2.5 mmol), and the mixture was stirred overnight at room temperature. After the reaction mixture was concentrated under reduced pressure, the obtained oily residue was dissolved in ethyl acetate (50 ml). The organic layer was washed successively with a 5% aqueous solution of sodium hydrogen carbonate and a saturated aqueous solution of sodium chloride, and then dried over anhydrous magnesium sulfate. After the drying agent was filtered off, the organic layer was concentrated under reduced pressure. The obtained oily residue was purified by silica gel column chromatography (hexane/ethyl acetate=5/1), followed by trituration with hexane to give 9-(3,3,3-trifluoro-2-hydroxy-2-methylpropanoylamino)-4,10-dihydrothieno[3,2-c][1]benzothiepin-10-one (0.60 g, 63%).

出典