Sodium hydride → 4-Chloro-2-[[(2,3-difluorophenyl)methyl]thio]-6-[(2-phenyl-1,3-dioxan-5-yl)oxy]-pyrimidine

HRID 2388730Notes

Reaction equation

HRID 2388730 reaction equation
[C:1]1([CH:7]2[O:12][CH2:11][CH:10]([OH:13])[CH2:9][O:8]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[H-].[Na+].[Cl:16][C:17]1[CH:22]=[C:21](Cl)[N:20]=[C:19]([S:24][CH2:25][C:26]2[CH:31]=[CH:30][CH:29]=[C:28]([F:32])[C:27]=2[F:33])[N:18]=1>O1CCCC1.O>[Cl:16][C:17]1[CH:22]=[C:21]([O:13][CH:10]2[CH2:11][O:12][CH:7]([C:1]3[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=3)[O:8][CH2:9]2)[N:20]=[C:19]([S:24][CH2:25][C:26]2[CH:31]=[CH:30][CH:29]=[C:28]([F:32])[C:27]=2[F:33])[N:18]=1

Participants

6

Reactant 3

HCID 24758Sodium hydrideHCID 743621,3-Dioxan-5-ol, 2-phenyl-HCID 859280374,6-Dichloro-2-((2,3-difluorobenzyl)thio)pyrimidine2×

Product 1

HCID 536283394-Chloro-2-[[(2,3-difluorophenyl)methyl]thio]-6-[(2-phenyl-1,3-dioxan-5-yl)oxy]-pyrimidine

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 2-phenyl-1,3-dioxan-5-ol (484 mg) in anhydrous tetrahydrofuran (10 ml) at 0° C. was added 60% sodium hydride (110 mg) and the mixture was heated to reflux for 25 minutes. On allowing to cool to ambient temperature 4,6-Dichloro-2-[(2,3-difluorobenzyl)thio]pyrimidine (the product of step (ii) (75 mg) was added and the reaction was heated to reflux for a further 90 minutes. The reaction mixture was allowed to cool, diluted with water and extracted with ethyl acetate (×3). The combined organic layers were dried with magnesium sulfate, filtered and evaporated. The residue was purified by column chromatography on silica using a 95:5 to 90:10 mixture of iso-hexane and ethyl acetate as eluent to give the sub-title compound as a white solid. Yield: 350 mg

Workup

  1. temperaturethe mixture was heated
  2. temperatureto reflux for 25 minutes
  3. additionwas added
  4. temperaturethe reaction was heated
  5. temperatureto reflux for a further 90 minutes
  6. temperatureto cool
  7. extractionextracted with ethyl acetate (×3)
  8. dry with materialThe combined organic layers were dried with magnesium sulfate
  9. filtrationfiltered
  10. customevaporated
  11. customThe residue was purified by column chromatography on silica using a 95:5
  12. additionto 90:10 mixture of iso-hexane and ethyl acetate as eluent

Sources & evidence

ORD record
ord-b5bbedbcf97e4721a113233a289260b7
Source dataset
uspto-grants-2012_09
Patent number
US08269002B2

Reaction notes

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