Thionyl Chloride → 9-(3,3,3-Trifluoro-2-hydroxy-2-methylpropanoylamino)-4,10-dihydrothieno[3,2-c][1]benzothiepin-10-one

HRID 322230노트

반응식

HRID 322230 반응식
[F:1][C:2]([F:10])([F:9])[C:3]([OH:8])([CH3:7])[C:4](O)=[O:5].S(Cl)(Cl)=O.[NH2:15][C:16]1[C:21]2[C:22](=[O:30])[C:23]3[S:29][CH:28]=[CH:27][C:24]=3[CH2:25][S:26][C:20]=2[CH:19]=[CH:18][CH:17]=1>CC(N(C)C)=O>[F:1][C:2]([F:10])([F:9])[C:3]([OH:8])([CH3:7])[C:4]([NH:15][C:16]1[C:21]2[C:22](=[O:30])[C:23]3[S:29][CH:28]=[CH:27][C:24]=3[CH2:25][S:26][C:20]=2[CH:19]=[CH:18][CH:17]=1)=[O:5]

참가 물질

5

반응물 3

HCID 24386Thionyl ChlorideHCID 27751253,3,3-Trifluoro-2-hydroxy-2-methylpropanoic acidHCID 15524296HCID 15524296, 화합물

생성물 1

HCID 155242979-(3,3,3-Trifluoro-2-hydroxy-2-methylpropanoylamino)-4,10-dihydrothieno[3,2-c][1]benzothiepin-10-one수율 63%

시약·촉매·용매 1

HCID 31374Dimethylacetamide용매

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온도
-10 °C

실험 절차

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%).

후처리

  1. additionwas added
  2. stirringthe mixture was stirred overnight at room temperature
  3. concentrationAfter the reaction mixture was concentrated under reduced pressure
  4. dissolutionthe obtained oily residue was dissolved in ethyl acetate (50 ml)
  5. washThe organic layer was washed successively with a 5% aqueous solution of sodium hydrogen carbonate
  6. dry with materiala saturated aqueous solution of sodium chloride, and then dried over anhydrous magnesium sulfate
  7. filtrationAfter the drying agent was filtered off
  8. concentrationthe organic layer was concentrated under reduced pressure
  9. customThe obtained oily residue was purified by silica gel column chromatography (hexane/ethyl acetate=5/1)

출처 및 근거

ORD 기록
ord-42c23ed998294d678c9e48731ddfb672
출처 데이터셋
uspto-grants-2001_04
특허 번호
US06211227B1

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