Ethylene Glycol → 2-[(2,5-Difluorophenyl)-hydroxymethyl]-5-(1,3-dioxolan-2-yl)pyridine

HRID 748833Notes

Reaction equation

HRID 748833 reaction equation
[N:1]1[CH:6]=[CH:5][CH:4]=CC=1.[Si](O[CH2:15][CH2:16][CH:17](C)[CH:18]([C:29]1[CH:34]=[C:33]([F:35])[CH:32]=[CH:31][C:30]=1[F:36])S(C1C=CC(Cl)=CC=1)(=O)=O)(C(C)(C)C)(C)C.[CH2:38]([OH:41])[CH2:39][OH:40].[BH4-].[Na+].[OH2:44]>>[F:36][C:30]1[CH:31]=[CH:32][C:33]([F:35])=[CH:34][C:29]=1[CH:18]([OH:44])[C:17]1[CH:16]=[CH:15][C:5]([CH:4]2[O:41][CH2:38][CH2:39][O:40]2)=[CH:6][N:1]=1

Participants

6

Reactant 5

HCID 174Ethylene GlycolHCID 962WaterHCID 1049PyridineHCID 4311764Sodium borohydrideHCID 59750761HCID 59750761, compound2×

Product 1

HCID 231146792-[(2,5-Difluorophenyl)-hydroxymethyl]-5-(1,3-dioxolan-2-yl)pyridineYield 52%

Conditions

Temperature
90 °C

Procedure

To a pyridine solution (60 ml) of the 5-dibromomethyl-2-(2,5-difluorobenzoyl)pyridine (Compound A) (3.91 g, 10 ml) obtained in Referential Example 45 was added ethylene glycol (6.2 g, 100 mmol). While heating at 90° C., the mixture was stirred for 17 hours. The reaction mixture was concentrated under reduced pressure and the residue was dissolved in ether (200 ml). The resulting solution was washed with water, a saturated aqueous solution of sodium bicarbonate and brine and dried over anhydrous magnesium sulfate. The solution was concentrated under reduced pressure. The residue was dissolved in ethanol (60 ml). Sodium borohydride (190 mg, 5 mmol) was added to the resulting solution under ice cooling, followed by stirring at room temperature for 1 hour. After the addition of water, the mixture was extracted with ethyl acetate. The solution was washed with brine and then dried over anhydrous magnesium sulfate. The residue obtained by concentrating the solution under reduced pressure was purified by silica gel chromatography (hexane:ethyl acetate=5:1-1:1) to yield the title compound (1.52 g, 52%) as an oil.

Workup

  1. concentrationThe reaction mixture was concentrated under reduced pressure
  2. dissolutionthe residue was dissolved in ether (200 ml)
  3. washThe resulting solution was washed with water
  4. dry with materiala saturated aqueous solution of sodium bicarbonate and brine and dried over anhydrous magnesium sulfate
  5. concentrationThe solution was concentrated under reduced pressure
  6. dissolutionThe residue was dissolved in ethanol (60 ml)
  7. stirringby stirring at room temperature for 1 hour
  8. extractionthe mixture was extracted with ethyl acetate
  9. washThe solution was washed with brine
  10. dry with materialdried over anhydrous magnesium sulfate
  11. customThe residue obtained
  12. concentrationby concentrating the solution under reduced pressure
  13. customwas purified by silica gel chromatography (hexane:ethyl acetate=5:1-1:1)

Sources & evidence

ORD record
ord-369583f482034a83b5ef7ccb350e429b
Source dataset
uspto-grants-2008_07
Patent number
US07399775B2

Reaction notes

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