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

HRID 1259331Notes

Reaction equation

HRID 1259331 reaction equation
P(Cl)(Cl)([Cl:3])=O.[Br:6][C:7]1[CH:8]=[N:9][CH:10]=[C:11]([O:13][CH2:14][CH3:15])[CH:12]=1>C(Cl)Cl.[Cl-].[Na+].O>[Br:6][C:7]1[CH:12]=[C:11]([O:13][CH2:14][CH3:15])[C:10]([Cl:3])=[N:9][CH:8]=1

Participants

5

Reactant 2

HCID 24813Phosphorus oxychlorideHCID 122934803-Bromo-5-ethoxypyridine

Product 1

HCID 713036735-Bromo-2-chloro-3-ethoxypyridineYield 85.6%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 57417360Sodium chloride; waterSolvent

Procedure

As shown in step 2-iv of Scheme 2, phosphorous oxychloride (48.02 g, 403.6 mmol) was added to 3-bromo-5-ethoxypyridine, 1-oxide (4.4 g, 20.18 mmol) in 700 mL of DCM at RT. The reaction mixture was stirred at RT overnight. After the addition of brine, the organics were partitioned, dried over MgSO4, filtered, and the filtrate concentrated under reduced pressure. The product was purified by filtering the concentrate through a pad of silica gel and eluting the pad with ethyl acetate. The volatiles were removed under reduced pressure to provide 5-bromo-2-chloro-3-ethoxypyridine (Compound 2003, 4.3 g, 85.6%): 1H NMR (CDCl3) δ 8.1 (s, 1H), 7.32 (s, 1H), 4.15 (q, 2H), 1.6 (t, 3H).

Workup

  1. customthe organics were partitioned
  2. dry with materialdried over MgSO4
  3. filtrationfiltered
  4. concentrationthe filtrate concentrated under reduced pressure
  5. customThe product was purified
  6. filtrationby filtering the
  7. concentrationconcentrate through a pad of silica gel
  8. washeluting the pad with ethyl acetate
  9. customThe volatiles were removed under reduced pressure

Sources & evidence

ORD record
ord-71809886b30047179b1044697afd1582
Source dataset
uspto-grants-2013_06
Patent number
US08466288B2

Reaction notes

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