Dimethylformamide → 5-Bromo-2,3-bis(methoxymethoxy)pyridine

HRID 709055Notes

Reaction equation

HRID 709055 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]([OH:9])[C:5]([OH:8])=[N:6][CH:7]=1.[H-].[Na+].[CH3:12][O:13][CH2:14]Cl.[C:16](=[O:19])([O-])[O-].[Na+].[Na+].[CH3:22]N(C=O)C>>[Br:1][C:2]1[CH:3]=[C:4]([O:9][CH2:22][O:19][CH3:16])[C:5]([O:8][CH2:12][O:13][CH3:14])=[N:6][CH:7]=1

Participants

6

Reactant 5

HCID 6228DimethylformamideHCID 7864Chloromethyl Methyl Ether2×HCID 10340Sodium CarbonateHCID 24758Sodium hydride2×HCID 178515448HCID 178515448, compound

Product 1

HCID 867315425-Bromo-2,3-bis(methoxymethoxy)pyridineYield 51%

Procedure

To a suspension of 5-bromopyridine-2,3-diol (9.4 g, 49.5 mmol) in DMF (165 ml) at 0° C. was added sodium hydride (1.18 g, 29.5 mmol) portion-wise and the reaction stirred for one hour at this temperature. Methoxymethyl chloride (3.8 ml, 49.5 mmol) was then added and the reaction stirred for a further 2 hours at 0° C. Sodium hydride (1.18 g, 29.5 mmol) was added and the reaction stirred for an hour at 0° C. before a further portion of methoxymethyl chloride (3.8 ml, 49.5 mmol) was added and the whole was allowed to warm and stirred for 16 hours. Upon cooling to room temperature the mixture was poured into cold saturated aqueous sodium carbonate solution. The organic materials were extracted into ethyl acetate and the layers separated before the aqueous phase, was extracted with ethyl acetate and the combined organics were then washed with brine (×7), dried (MgSO4) and concentrated in vacuo. The crude product was purified by column chromatography (SiO2; 0-100% ethyl acetate/petrol) to yield 5-bromo-2,3-bis(methoxymethoxy)pyridine (7.03 g, 51%).

Workup

  1. stirringthe reaction stirred for a further 2 hours at 0° C
  2. additionwas added
  3. temperatureto warm
  4. stirringstirred for 16 hours
  5. extractionThe organic materials were extracted into ethyl acetate
  6. customthe layers separated before the aqueous phase
  7. extractionwas extracted with ethyl acetate
  8. washthe combined organics were then washed with brine (×7)
  9. dry with materialdried (MgSO4)
  10. concentrationconcentrated in vacuo
  11. customThe crude product was purified by column chromatography (SiO2; 0-100% ethyl acetate/petrol)

Sources & evidence

ORD record
ord-3dc1f25244d6429eb362319086ddf84b
Source dataset
uspto-grants-2015_11
Patent number
US09180122B2

Reaction notes

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