Thionyl Chloride → 2-Chloromethyl-6-(5-methyl-2-phenyl-4-oxazolylmethoxy)pyridine

HRID 1294142Notes

Reaction equation

HRID 1294142 reaction equation
[CH3:1][C:2]1[O:6][C:5]([C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=2)=[N:4][C:3]=1[CH2:13][O:14][C:15]1[N:20]=[C:19]([C:21](OC)=O)[CH:18]=[CH:17][CH:16]=1.[H-].[Al+3].[Li+].[H-].[H-].[H-].O.O.O.O.O.O.O.O.O.O.[O-]S([O-])(=O)=O.[Na+].[Na+].S(Cl)([Cl:50])=O>O1CCCC1>[Cl:50][CH2:21][C:19]1[CH:18]=[CH:17][CH:16]=[C:15]([O:14][CH2:13][C:3]2[N:4]=[C:5]([C:7]3[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=3)[O:6][C:2]=2[CH3:1])[N:20]=1

Participants

6

Reactant 4

HCID 24386Thionyl ChlorideHCID 62649Sodium sulfate decahydrateHCID 17861391Methyl 6-(5-methyl-2-phenyl-4-oxazolyl)methoxy-2-pyridinecarboxylateHCID 21226445Aluminium lithium hydride

Product 1

HCID 178613022-Chloromethyl-6-(5-methyl-2-phenyl-4-oxazolylmethoxy)pyridine

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a mixture of methyl 6-(5-methyl-2-phenyl-4-oxazolyl)methoxy-2-pyridinecarboxylate (6.49 g) and tetrahydrofuran (60 mL) was added lithium aluminum hydride (0.759 g) under ice-cooling, and the mixture was stirred at room temperature for 30 min. To the mixture was added sodium sulfate 10 hydrate (6.44 g) and further stirred at room temperature for 30 min. The insoluble materials were removed by filtration, and the filtrate was concentrated to give crystals. The obtained crystals were added to thionyl chloride (20 mL) under ice-cooling, and the mixture was stirred at room temperature for 1 hr. The reaction mixture was concentrated, saturated aqueous sodium hydrogencarbonate was added to the residue and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate, and concentrated. The obtained residue was subjected to silica gel column chromatography to give crystals of 2-chloromethyl-6-(5-methyl-2-phenyl-4-oxazolylmethoxy)pyridine from a fraction eluted with ethyl acetate-hexane (1:3, v/v). Recrystallization from ethyl acetate-hexane gave colorless plate crystals (2.74 g, 44%). melting point: 85-86° C.

Workup

  1. temperaturecooling
  2. stirringfurther stirred at room temperature for 30 min
  3. customThe insoluble materials were removed by filtration
  4. concentrationthe filtrate was concentrated
  5. customto give crystals
  6. temperaturecooling
  7. stirringthe mixture was stirred at room temperature for 1 hr
  8. concentrationThe reaction mixture was concentrated
  9. additionsaturated aqueous sodium hydrogencarbonate was added to the residue
  10. extractionthe mixture was extracted with ethyl acetate
  11. washThe organic layer was washed with saturated brine
  12. dry with materialdried over anhydrous magnesium sulfate
  13. concentrationconcentrated

Sources & evidence

ORD record
ord-8a8317de88994b77a68b9854d29b03b8
Source dataset
uspto-grants-2007_07
Patent number
US07238716B2

Reaction notes

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