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

HRID 2080365Notes

Reaction equation

HRID 2080365 reaction equation
N1C=CC=CC=1.Br[CH:8](Br)[C:9]1[CH:10]=[CH:11][C:12]([C:15](=[O:24])[C:16]2[CH:21]=[C:20]([F:22])[CH:19]=[CH:18][C:17]=2[F:23])=[N:13][CH:14]=1.[CH2:26]([OH:29])[CH2:27][OH:28].[BH4-].[Na+]>CCOCC.C(O)C.O>[F:23][C:17]1[CH:18]=[CH:19][C:20]([F:22])=[CH:21][C:16]=1[CH:15]([OH:24])[C:12]1[CH:11]=[CH:10][C:9]([CH:8]2[O:29][CH2:26][CH2:27][O:28]2)=[CH:14][N:13]=1

Participants

8

Reactant 4

HCID 174Ethylene GlycolHCID 1049PyridineHCID 4311764Sodium borohydrideHCID 23028691[5-(Dibromomethyl)pyridin-2-yl](2,5-difluorophenyl)methanone2×

Product 1

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

Reagents, catalysts & solvents 3

HCID 702EthanolSolventHCID 962WaterSolventHCID 3283Diethyl EtherSolvent

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 mmol) obtained in Referential Example 20 was added ethylene glycol (6.2 g, 100 mmol). While heating at 90° C., the resulting mixture was stirred for 17 hours. The reaction mixture was concentrated under reduced pressure. The residue thus obtained was dissolved in ether (200 ml). The resulting solution was washed with water, a saturated aqueous solution of sodium bicarbonate and brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue thus obtained was dissolved in ethanol (60 ml). To the resulting solution was added sodium borohydride (190 mg, 5 mmol) under ice cooling. The resulting mixture was stirred at room temperature for 1 hour. After the addition of water, the mixture was extracted with ethyl acetate. The extract was washed with brine, dried over anhydrous magnesium sulfate, and then concentrated under reduced pressure. The residue thus obtained was purified by silica gel chromatography (hexane:ethyl acetate=5:1 to 1:1) to give the title compound (1.52 g, 52%) as an oil.

Workup

  1. concentrationThe reaction mixture was concentrated under reduced pressure
  2. customThe residue thus obtained
  3. washThe resulting solution was washed with water
  4. dry with materiala saturated aqueous solution of sodium bicarbonate and brine, dried over anhydrous magnesium sulfate
  5. concentrationconcentrated under reduced pressure
  6. customThe residue thus obtained
  7. stirringThe resulting mixture was stirred at room temperature for 1 hour
  8. extractionthe mixture was extracted with ethyl acetate
  9. washThe extract was washed with brine
  10. dry with materialdried over anhydrous magnesium sulfate
  11. concentrationconcentrated under reduced pressure
  12. customThe residue thus obtained
  13. customwas purified by silica gel chromatography (hexane:ethyl acetate=5:1 to 1:1)

Sources & evidence

ORD record
ord-8060e4c275c74b09ad15b1a3719ef165
Source dataset
uspto-grants-2011_04
Patent number
US07932271B2

Reaction notes

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