Phenol → 5-Chloro-3-phenoxy-2-pyridinamine

HRID 335073Notes

Reaction equation

HRID 335073 reaction equation
Br[C:2]1[C:3]([NH2:9])=[N:4][CH:5]=[C:6]([Cl:8])[CH:7]=1.[C:10]1([OH:16])[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1.OC1C=CC=CC=1/C=N/O.C([O-])([O-])=O.[Cs+].[Cs+]>CN(C=O)C.[Cu-]=O>[Cl:8][C:6]1[CH:7]=[C:2]([O:16][C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)[C:3]([NH2:9])=[N:4][CH:5]=1

Participants

7

Reactant 4

HCID 996PhenolHCID 10796Cesium carbonateHCID 27639713-Bromo-5-chloropyridin-2-amineHCID 135408751Salicylaldoxime

Product 1

HCID 187528795-Chloro-3-phenoxy-2-pyridinamineYield 15%

Reagents, catalysts & solvents 2

HCID 178419072HCID 178419072, compoundCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
110 °C

Procedure

3-Bromo-5-chloropyridin-2-amine (50.0 g, 241 mmol), phenol (45.4 g, 482 mmol), copper(I)oxide (1.72 g, 12.1 mmol), (E)-2-hydroxybenzaldehyde oxime (6.61 g, 48.2 mmol), Cs2CO3 (157 g, 482 mmol), and 3A powdered molecular (72.3 g) sieves were placed in DMF (300 mL) and heated at 110° C. for 3 days. Reaction was cooled, then filtered through celite. Reaction was then partitioned between water and ether. An emulsion was formed and was filtered through a plug of celite. Water was extracted with ether then dried, filtered, and concentrated. Crude material was purified on a first silica gel chromatography (5-10% EtOAc in hexanes), and then on a second column to provide the title compound (8.00 g, 15.0% yield). 1H NMR (CDCl3) δ 7.80 (d, 1H), 7.39 (t, 2H), 7.19 (t, 1H), 7.03 (d, 2H), 6.94 (d, 1H), 4.76 (bs, 2H); Mass spectrum (apci) m/z=221 (100).

Workup

  1. customReaction
  2. temperaturewas cooled
  3. filtrationfiltered through celite
  4. customReaction
  5. customwas then partitioned between water and ether
  6. customAn emulsion was formed
  7. filtrationwas filtered through a plug of celite
  8. extractionWater was extracted with ether
  9. customthen dried
  10. filtrationfiltered
  11. concentrationconcentrated
  12. customCrude material was purified on a first silica gel chromatography (5-10% EtOAc in hexanes)

Sources & evidence

ORD record
ord-e103d3f542a046f7a035fd939ea83912
Source dataset
uspto-grants-2014_11
Patent number
US08883828B2

Reaction notes

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