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

HRID 39351Notes

Reaction equation

HRID 39351 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 1003, 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-af269c774d2d45fcb39315d5e1161463
Source dataset
uspto-grants-2013_09
Patent number
US08524906B2

Reaction notes

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