Sodium hydride → Tyrima

HRID 1872881Notes

Reaction equation

HRID 1872881 reaction equation
[F:1][C:2]1[CH:3]=[CH:4][C:5]2[S:6](=[O:18])(=[O:17])[C:7]3[C:12]([O:13][C:14]=2[CH:15]=1)=[CH:11][C:10]([OH:16])=[CH:9][CH:8]=3.[H-].[Na+].I[CH2:22][C:23]([F:26])([F:25])[F:24]>CN(C)C=O>[F:1][C:2]1[CH:3]=[CH:4][C:5]2[S:6](=[O:18])(=[O:17])[C:7]3[C:12]([O:13][C:14]=2[CH:15]=1)=[CH:11][C:10]([O:16][CH2:22][C:23]([F:26])([F:25])[F:24])=[CH:9][CH:8]=3

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 677091,1,1-Trifluoro-2-iodoethaneHCID 18687725HCID 18687725, compound

Product 1

HCID 18687754TyrimaYield 51.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Solid 3-fluoro-7-hydroxyphenoxathiin 10,10-dioxide (Example 64) (1.092 g, 4.10 mmoles) was added to an ice-bath cooled, stirred mixture of sodium hydride (60% dispersion in mineral oil) (Aldrich) (0.164 g, 4.10 mmole) in N,N-dimethylformamide (20 mL). After 10 minutes, within which effervescence ceased, 2-iodo-1,1,1-trifluoroethaane (4.993 g, 23.78 mmoles) was added and the solution was heated with stirring at 100° C. for 24 hours. The reaction was cooled and added in portions to 100 mL of vigorously stirred ice-water to give a solid, which was collected by suction filtration and washed with water. The solid which was two equal size spots on tlc (silica gel, ethyl acetate-hexanes:1-4) dissolved in dichloromethane (50 mL), absorbed on silica gel 60 and purified by flash column chromatography on silica gel 60. The column was eluted with ethyl acetate-hexanes:1-6 (1 L) and ethyl acetate-hexanes:1-3 (1 L), and the fractions that contained product (the higher Rf spot on tlc) were combined and spin evaporated in vacuo to give 0.731 g (51% yield) of 3-fluoro-7-(2,2,2-trifluoroethoxy)phenoxathiin 10,10-dioxide as a white powder, m.p. 160-161° C.

Workup

  1. temperaturecooled
  2. temperaturethe solution was heated
  3. stirringwith stirring at 100° C. for 24 hours
  4. temperatureThe reaction was cooled
  5. customto give a solid, which
  6. filtrationwas collected by suction filtration
  7. washwashed with water
  8. dissolutiondissolved in dichloromethane (50 mL)
  9. customabsorbed on silica gel 60
  10. custompurified by flash column chromatography on silica gel 60
  11. washThe column was eluted with ethyl acetate-hexanes
  12. customspin evaporated in vacuo

Sources & evidence

ORD record
ord-a0d63ffb6c214900b0c6811e86340fae
Source dataset
uspto-grants-2000_08
Patent number
US06110961

Reaction notes

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