Water → HCID 11789921, compound

HRID 1793317Notes

Reaction equation

HRID 1793317 reaction equation
Cl.[Cl:2][C:3]1[C:8]([OH:9])=[CH:7][CH:6]=[CH:5][N:4]=1.[H-].[Na+].Cl[CH2:13][CH:14]1[CH2:16][O:15]1.O>CN(C=O)C>[Cl:2][C:3]1[C:8]([O:9][CH2:13][CH:14]2[CH2:16][O:15]2)=[CH:7][CH:6]=[CH:5][N:4]=1

Participants

6

Reactant 4

HCID 962WaterHCID 7835EpichlorohydrinHCID 24758Sodium hydrideHCID 22020933HCID 22020933, compound

Product 1

HCID 11789921HCID 11789921, compoundYield 194.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent3×

Procedure

Reaction was carried out under nitrogen flow. A mixture of 2-chloro-3-pyridinol hydrochloride (1:1) (1.760 mol) in DMF (1000 ml) was added dropwise in 30 minutes to a mixture of NaH 60% (1.934 mol) in DMF (1200 ml) (temperature below 27° C.). The reaction mixture was stirred for 30 minutes. (Chloromethyl)-oxirane (3.530 mol) in DMF (1200 ml) was added dropwise over 30 minutes. The reaction mixture was stirred for 9 hours at 60° C. The mixture was cooled. Water was added dropwise on an ice bath. The mixture was extracted with DCM. The organic layer was dried, filtered and the solvent was evaporated. Petroleum ether was added to the residue, then decanted (3 times). This fraction was combined with analogously obtained fractions, then purified by HPLC over silica gel (eluent: hexane/ethyl acetate (50/50)). The desired fractions were collected and the solvent was evaporated, yielding 635 g of 2-chloro-3-(oxiranylmethoxy)-pyridine (intermediate 19).

Workup

  1. customReaction
  2. stirringThe reaction mixture was stirred for 9 hours at 60° C
  3. temperatureThe mixture was cooled
  4. extractionThe mixture was extracted with DCM
  5. customThe organic layer was dried
  6. filtrationfiltered
  7. customthe solvent was evaporated
  8. additionPetroleum ether was added to the residue
  9. customdecanted (3 times)
  10. custompurified by HPLC over silica gel (eluent: hexane/ethyl acetate (50/50))
  11. customThe desired fractions were collected
  12. customthe solvent was evaporated

Sources & evidence

ORD record
ord-d050e9c621754d0090d82aad60627c10
Source dataset
uspto-grants-2006_07
Patent number
US07081453B2

Reaction notes

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