Phosphorus oxychloride → 2-Chloro-4-[2-ethyl-4-(4-fluorophenyl)-1,3-thiazol-5-yl]pyridine

HRID 1496633Notes

Reaction equation

HRID 1496633 reaction equation
[CH2:1]([C:3]1[S:4][C:5]([C:15]2[CH:20]=[CH:19][N+:18]([O-])=[CH:17][CH:16]=2)=[C:6]([C:8]2[CH:13]=[CH:12][C:11]([F:14])=[CH:10][CH:9]=2)[N:7]=1)[CH3:2].P(Cl)(Cl)([Cl:24])=O>>[Cl:24][C:19]1[CH:20]=[C:15]([C:5]2[S:4][C:3]([CH2:1][CH3:2])=[N:7][C:6]=2[C:8]2[CH:13]=[CH:12][C:11]([F:14])=[CH:10][CH:9]=2)[CH:16]=[CH:17][N:18]=1

Participants

3

Reactant 2

HCID 24813Phosphorus oxychlorideHCID 675374444-[2-Ethyl-4-(4-fluorophenyl)-1,3-thiazol-5-yl]pyridine 1-oxide

Product 1

HCID 866431432-Chloro-4-[2-ethyl-4-(4-fluorophenyl)-1,3-thiazol-5-yl]pyridine

Procedure

A mixture of 1.90 g (6.33 mmol) of 4-[2-ethyl-4-(4-fluorophenyl)-1,3-thiazol-5-yl]pyridine 1-oxide and 40 ml of phosphoryl chloride is heated under reflux. After 8 h, the reaction mixture is concentrated under reduced pressure, the residue is taken up in 150 ml of dichloromethane and 50 ml of ice-water are added. The organic phase is separated off and once more washed with 50 ml of water, dried over MgSO4 and freed from the solvent under reduced pressure. The residue is then purified by column chromatography on silica gel (cyclohexane/ethyl acetate). This gives 1.35 g (65%) of the desired product; 1H-NMR(DMSO-d6) δ: 8.35 (d, 1H), 7.49 (m, 2H), 7.35 (s, 1H), 7.25 (d, 1H), 7.19 (m, 2H), 3.06 (q, 2H), 1.37 (t, 3H).

Workup

  1. temperatureis heated
  2. temperatureunder reflux
  3. concentrationthe reaction mixture is concentrated under reduced pressure
  4. addition50 ml of ice-water are added
  5. customThe organic phase is separated off
  6. washonce more washed with 50 ml of water
  7. dry with materialdried over MgSO4
  8. customThe residue is then purified by column chromatography on silica gel (cyclohexane/ethyl acetate)

Sources & evidence

ORD record
ord-75ba65c429eb4ee5a4198be8c3e68731
Source dataset
uspto-grants-2015_12
Patent number
US09198426B2

Reaction notes

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