Phosphorus oxychloride → 4-Chloro-2-(2,6-dichloro-4-iodophenyl)-7-fluorothiazolo[5,4-c]pyridine

HRID 2366318Notes

Reaction equation

HRID 2366318 reaction equation
[Cl:1][C:2]1[CH:7]=[C:6]([I:8])[CH:5]=[C:4]([Cl:9])[C:3]=1[C:10]1[S:11][C:12]2[CH:13]=[N+:14]([O-])[CH:15]=[C:16]([F:19])[C:17]=2[N:18]=1.P(Cl)(Cl)([Cl:23])=O.C(=O)(O)[O-].[Na+]>ClCCCl>[Cl:23][C:13]1[C:12]2[S:11][C:10]([C:3]3[C:2]([Cl:1])=[CH:7][C:6]([I:8])=[CH:5][C:4]=3[Cl:9])=[N:18][C:17]=2[C:16]([F:19])=[CH:15][N:14]=1

Participants

5

Reactant 3

HCID 24813Phosphorus oxychlorideHCID 516892Sodium BicarbonateHCID 668013882-(2,6-Dichloro-4-iodophenyl)-7-fluorothiazolo[5,4-c]pyridine-5-oxide

Product 1

HCID 866690314-Chloro-2-(2,6-dichloro-4-iodophenyl)-7-fluorothiazolo[5,4-c]pyridineYield 34%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

To a suspension of 2-(2,6-dichloro-4-iodophenyl)-7-fluorothiazolo[5,4-c]pyridine-5-oxide (2.8 g, 6.4 mmol) in 1,2-dichloroethane (80 mL) was added phosphorus oxychloride (1.8 mL, 19.1 mmol). The reaction mixture was heated under reflux for 16 hours. Upon cooling, the resultant mixture was treated cautiously with aqueous sodium bicarbonate to achieve pH 6-7, and then extracted with dichloromethane (×2). The combined organic extracts were dried (MgSO4), filtered and concentrated under reduced pressure. The crude product was purified by column chromatography on silica gel eluting with 0-50% diethyl ether in petroleum ether to afford the title compound as a white solid (1.0 g, 34% yield). 1H NMR (400 MHz, CDCl3): δ 8.35 (d, J=1.5 Hz, 1H), 7.82 (s, 2H).

Workup

  1. temperatureThe reaction mixture was heated
  2. temperatureunder reflux for 16 hours
  3. temperatureUpon cooling
  4. extractionextracted with dichloromethane (×2)
  5. dry with materialThe combined organic extracts were dried (MgSO4)
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe crude product was purified by column chromatography on silica gel eluting with 0-50% diethyl ether in petroleum ether

Sources & evidence

ORD record
ord-059a07506a8d412f8bfd221b90ce2e05
Source dataset
uspto-grants-2014_04
Patent number
US08697708B2

Reaction notes

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