Thionyl Chloride → HCID 22010039, compound

HRID 322238Notes

Reaction equation

HRID 322238 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[CH:17]=[CH:18][C:19]2[CH2:25][O:24][C:23]3[CH:26]=[CH:27][C:28]([O:30][CH3:31])=[CH:29][C:22]=3[C:21](=[O:32])[C:20]=2[CH:33]=1>CC(N(C)C)=O>[CH3:31][O:30][C:28]1[CH:27]=[CH:26][C:23]2[O:24][CH2:25][C:19]3[CH:18]=[CH:17][C:16]([NH:15][C:4](=[O:5])[C:3]([OH:8])([CH3:7])[C:2]([F:10])([F:9])[F:1])=[CH:33][C:20]=3[C:21](=[O:32])[C:22]=2[CH:29]=1

Participants

5

Reactant 3

HCID 24386Thionyl ChlorideHCID 27751253,3,3-Trifluoro-2-hydroxy-2-methylpropanoic acidHCID 22010045HCID 22010045, compound

Product 1

HCID 22010039HCID 22010039, compoundYield 87%

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent

Conditions

Temperature
-10 °C

Procedure

In dimethylacetamide (8 ml) was dissolved 3,3,3-trifluoro-2-hydroxy-2-methylpropanoic acid (0.73 g, 4.63 mmol), and thionyl chloride (0.36 ml, 4.63 mmol) was added thereto at −15° C., followed by stirring at −15 to −5° C. for one hour. To the reaction mixture was added 9-amino-2-methoxy-6,11-dihydrodibenz[b,e]oxepin-11-one obtained in Reference Example 11 (0.59 g, 2.32 mmol), and the mixture was stirred overnight at room temperature. The reaction mixture was concentrated under reduced pressure, and the obtained oily residue was dissolved in ethyl acetate (25 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 substance was purified by silica gel column chromatography (hexane/ethyl acetate=3/1), followed by trituration with isopropyl ether to give Compound 1-48 (yield: 87%).

Workup

  1. additionwas added
  2. customat −15° C.
  3. stirringthe mixture was stirred overnight at room temperature
  4. concentrationThe reaction mixture was concentrated under reduced pressure
  5. dissolutionthe obtained oily residue was dissolved in ethyl acetate (25 ml)
  6. washThe organic layer was washed successively with a 5% aqueous solution of sodium hydrogen carbonate
  7. dry with materiala saturated aqueous solution of sodium chloride, and then dried over anhydrous magnesium sulfate
  8. filtrationAfter the drying agent was filtered off
  9. concentrationthe organic layer was concentrated under reduced pressure
  10. customThe obtained oily substance was purified by silica gel column chromatography (hexane/ethyl acetate=3/1)

Sources & evidence

ORD record
ord-b93b865da29a466da7342ee9f8654cf0
Source dataset
uspto-grants-2001_04
Patent number
US06211227B1

Reaction notes

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