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

HRID 322230Notes

Reaction equation

HRID 322230 reaction equation
[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]

Participants

5

Reactant 3

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

Product 1

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

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent

Conditions

Temperature
-10 °C

Procedure

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%).

Workup

  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)

Sources & evidence

ORD record
ord-42c23ed998294d678c9e48731ddfb672
Source dataset
uspto-grants-2001_04
Patent number
US06211227B1

Reaction notes

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