Phosphorus oxychloride → 5-Bromo-2-chloro-3-ethoxypyridine

HRID 1050112Notes

Reaction equation

HRID 1050112 reaction equation
[Br:1][C:2]1[CH:3]=[N+:4]([O-])[CH:5]=[C:6]([O:8][CH2:9][CH3:10])[CH:7]=1.O=P(Cl)(Cl)[Cl:14]>C(Cl)Cl>[Br:1][C:2]1[CH:7]=[C:6]([O:8][CH2:9][CH3:10])[C:5]([Cl:14])=[N:4][CH:3]=1

Participants

4

Reactant 2

HCID 24813Phosphorus oxychlorideHCID 53497593Pyridine, 3-bromo-5-ethoxy-, 1-oxide

Product 1

HCID 713036735-Bromo-2-chloro-3-ethoxypyridineYield 33.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
45 °C

Procedure

To a solution of 3-bromo-5-ethoxypyridine-1-oxide (40 g, 183 mmol) in DCM (200 mL) at 0° C. was slowly added POCl3 (159 mL, 1701 mmol) over 30 min. Then the resulting solution was warmed to 45° C. and stirred for 15 h. The mixture was concentrated and adjusted pH=9-10 with 10% NaOH solution, extracted with DCM (300 mL×2), dried over Na2SO4, filtered, and concentrated to give the crude product which was purified by silica column chromatography (10% EA: 90% PE, 800 g silica column). All fractions found to contain product by TLC (EA: PE=1:5, Rf=0.6) were combined and concentrated to yield an oil of 5-bromo-2-chloro-3-ethoxypyridine (30 g, 60.9 mmol, 33% yield): 1H NMR (400 MHz, CD3OD) δ 8.00-7.99 (d, J=2.0 Hz, 1H), 7.65-7.64 (d, J=2.0 Hz, 1H), 4.17-4.12 (m, 2H), 1.44 (t, J=7.0 Hz, 2H); ES-LCMS m/z 235 (M+H).

Workup

  1. customat 0° C.
  2. customover 30 min
  3. concentrationThe mixture was concentrated
  4. extractionadjusted pH=9-10 with 10% NaOH solution, extracted with DCM (300 mL×2)
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customto give the crude product which
  9. customwas purified by silica column chromatography (10% EA: 90% PE, 800 g silica column)
  10. concentrationconcentrated

Sources & evidence

ORD record
ord-3c87d16ff2db42898743ad29f226be33
Source dataset
uspto-grants-2016_07
Patent number
US09382238B2

Reaction notes

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