Phosphorus oxychloride → 3-Bromo-4-chlorothieno(3,2-c)pyridine

HRID 1270838Notes

Reaction equation

HRID 1270838 reaction equation
[Br:1][C:2]1[C:6]2[C:7](=O)[NH:8][CH:9]=[CH:10][C:5]=2[S:4][CH:3]=1.O=P(Cl)(Cl)[Cl:14]>>[Br:1][C:2]1[C:6]2[C:7]([Cl:14])=[N:8][CH:9]=[CH:10][C:5]=2[S:4][CH:3]=1

Participants

3

Reactant 2

HCID 24813Phosphorus oxychlorideHCID 184507963-Bromothieno[3,2-c]pyridin-4(5H)-one

Product 1

HCID 184507733-Bromo-4-chlorothieno(3,2-c)pyridine

Procedure

A suspension of Example 1A (35.91 g, 0.156 mol) in POCl3 (80 mL) was heated to reflux for 2.5 hours, cooled to room temperature, poured onto 800 g of ice, and extracted repeatedly with dichloromethane. The combined extracts were washed with water and brine, dried (Na2SO4), filtered, and concentrated. The residue was purified by flash column chromatography on silica gel with 0 to 5% methanol/dichloromethane to provide 29.3 g of 3-bromo-4-chlorothieno[3,2-c]pyridine (mp 158–159° C.), which was diluted with dioxane (500 mL) and concentrated aqueous NH3 (500 mL), heated to 150° C. under pressure (260 psi) for 20 hours, and concentrated. The residue was triturated from MTBE then from methanol to provide 20.29 g of the desired product. m.p. 153–155° C.

Workup

  1. temperatureto reflux for 2.5 hours
  2. extractionextracted repeatedly with dichloromethane
  3. washThe combined extracts were washed with water and brine
  4. dry with materialdried (Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe residue was purified by flash column chromatography on silica gel with 0 to 5% methanol/dichloromethane

Sources & evidence

ORD record
ord-6c6c179ea4e349b984e547d200601720
Source dataset
uspto-grants-2007_04
Patent number
US07202363B2

Reaction notes

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