Phosphorus oxychloride → 4-Chloro-3-[3-(methyloxy)phenyl]thieno[2,3-b]pyridine

HRID 573567

Reaction equation

HRID 573567 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]([C:9]2[C:17]3[C:16](=O)[CH:15]=[CH:14][NH:13][C:12]=3[S:11][CH:10]=2)[CH:6]=[CH:7][CH:8]=1.P(Cl)(Cl)([Cl:21])=O>>[Cl:21][C:16]1[CH:15]=[CH:14][N:13]=[C:12]2[S:11][CH:10]=[C:9]([C:5]3[CH:6]=[CH:7][CH:8]=[C:3]([O:2][CH3:1])[CH:4]=3)[C:17]=12

Participants

3

Reactant 2

HCID 24813Phosphorus oxychlorideHCID 683240213-[3-(Methyloxy)phenyl]thieno[2,3-b]pyridin-4(7H)-one

Product 1

HCID 683237304-Chloro-3-[3-(methyloxy)phenyl]thieno[2,3-b]pyridineYield 85.1%

Conditions

Temperature
110 °C

Procedure

A mixture of 3-[3-(methyloxy)phenyl]thieno[2,3-b]pyridin-4(7H)-one (Description 42) (465 mg, 1.807 mmol) and phosphorus oxychloride (5 mL, 53.6 mmol) was heated at 110° C. for 1 h. After cooling to RT, the mixture was poured onto ice, stirred for 30 min and then extracted with DCM (10 mL×3). The organic layers were combined, washed with saturated NaHCO3 solution (100 mL), brine (100 mL), filtered through phase separator and evaporated in vacuo. The residue was purified by chromatography on silica, eluting with a gradient of 0-40% ethyl acetate in cyclohexane, to give the title compound (424 mg). LCMS (A) m/z: 278 [M+1]+, Rt 1.33 min (acidic).

Workup

  1. temperatureAfter cooling to RT
  2. additionthe mixture was poured onto ice
  3. extractionextracted with DCM (10 mL×3)
  4. washwashed with saturated NaHCO3 solution (100 mL), brine (100 mL)
  5. filtrationfiltered through phase separator
  6. customevaporated in vacuo
  7. customThe residue was purified by chromatography on silica
  8. washeluting with a gradient of 0-40% ethyl acetate in cyclohexane

Sources & evidence

ORD record
ord-064ceb6aef93410ba0815f911a6328a6
Source dataset
uspto-grants-2015_05
Patent number
US09029545B2

Linked notes

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