Sodium Hydroxide → 2-broMo-3-(difluoroMethoxy)pyridine

HRID 538438Notes

Reaction equation

HRID 538438 reaction equation
[Br:1][C:2]1[C:7]([OH:8])=[CH:6][CH:5]=[CH:4][N:3]=1.Cl[C:10]([F:15])([F:14])C([O-])=O.[Na+].[OH-].[Na+]>CN(C=O)C>[Br:1][C:2]1[C:7]([O:8][CH:10]([F:15])[F:14])=[CH:6][CH:5]=[CH:4][N:3]=1

Participants

5

Reactant 3

HCID 14798Sodium HydroxideHCID 230702-Bromo-3-pyridinolHCID 2734985Sodium chlorodifluoroacetate

Product 1

HCID 580424482-broMo-3-(difluoroMethoxy)pyridineYield 43%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
55 °C

Procedure

A mixture of 2-bromopyridin-3-ol (3.55 g, 20.4 mmol), sodium chlorodifluoroacetate (6.22 g, 40.8 mmol), and NaOH (0.90 g, 22.4 mmol) in DMF (20 ml) was heated at 55° C. for 111 h. The reaction was allowed to cool to rt and concentrated, and resulting residue was partitioned between EtOAc/sat. Na2CO3 (80 ml/40 ml). The organic phase was collected and washed with brine (40 ml), dried (Na2SO4), concentrated and the resulting residue was purified by flash chromatography (SiO2, 100:0-0:100 hexanes-EtOAc) to provide 1.95 g (43%) of 2-bromo-3-(difluoromethoxy)pyridine: LCMS (m/z, MH+): 225.9, tR=0.74 min; 1H NMR (CDCl3, 400 MHz) δ 8.23-8.33 (m, 1H), 7.52-7.60 (m, 1H), 7.27-7.35 (m, 1H), 6.60 (t, J=72.4 Hz, 1H).

Workup

  1. temperatureto cool to rt
  2. concentrationconcentrated
  3. customresulting residue
  4. customwas partitioned between EtOAc/
  5. customThe organic phase was collected
  6. washwashed with brine (40 ml)
  7. dry with materialdried (Na2SO4)
  8. concentrationconcentrated
  9. customthe resulting residue was purified by flash chromatography (SiO2, 100:0-0:100 hexanes-EtOAc)

Sources & evidence

ORD record
ord-c2f3cc3133e44dc5a4c9c6787ff6f18b
Source dataset
uspto-grants-2014_10
Patent number
US08865732B2

Reaction notes

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