Reaction #67629

Reaction equation

phosphorous oxychloride

3-bromo-5-ethoxypyridine

→

5-bromo-2-chloro-3-ethoxypyridine

Yield 85.6%

Solvents

brine

DCM

Conditions

Workup

1. 1
   Otherthe organics were partitioned
2. 2
   Dryingdried over MgSO4
3. 3
   Filtrationfiltered
4. 4
   Concentrationthe filtrate concentrated under reduced pressure
5. 5
   OtherThe product was purified
6. 6
   Filtrationby filtering the
7. 7
   Concentrationconcentrate through a pad of silica gel
8. 8
   Washeluting the pad with ethyl acetate
9. 9
   OtherThe volatiles were removed under reduced pressure

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).

Source