Phosphorus oxychloride → 7-Chlorothieno[3,2-b]pyridine

HRID 1676232Notes

Reaction equation

HRID 1676232 reaction equation
O=P(Cl)(Cl)Cl.[S:6]1[C:14]2[C:9](=[N:10][CH:11]=[CH:12][C:13]=2O)[CH:8]=[CH:7]1.C(Cl)(=O)C([Cl:19])=O>ClCCCl>[Cl:19][C:13]1[CH:12]=[CH:11][N:10]=[C:9]2[CH:8]=[CH:7][S:6][C:14]=12

Participants

5

Reactant 3

HCID 24813Phosphorus oxychlorideHCID 65578Oxalyl chlorideHCID 5074765Thieno[3,2-b]pyridin-7-ol

Product 1

HCID 112752517-Chlorothieno[3,2-b]pyridine

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

To a stirred solution of POCl3 (28.6 mL, 313 mmol) in 1,2-dichloroethane (200 mL) was added commercially available thieno[3,2-b]pyridin-7-ol (94.7 g, 626 mmol) as a powder in one portion. The reaction was stirred for 2 hours at reflux under N2. The mixture was concentrated, using toluene (3×100 mL) to azeotrope. The dark residue was resuspended in CH2Cl2 (1 L), and a saturated aqueous solution of NaHCO3 (500 mL) was carefully added. The mixture was stirred for 30 minutes until bubbling had ceased. The biphase was separated, and the aqueous was re-extracted with CH2Cl2 (500 mL). The combined organic phases were dried (Na2SO4), filtered, and concentrated, to obtain a brown oil, which crystallized upon standing (38.4 g, 71%). 7-Chlorothieno[3,2-b]pyridine has also been prepared using oxalyl chloride (WO 99/24440). 1H NMR (400 MHz, CDCl3) δ 8.61 (d, J=5 Hz, 1H), 7.80 (d, J=6 Hz, 1H), 7.60 (d, J=6 Hz, 1H), 7.29 (d, J=5 Hz, 1H).

Workup

  1. temperatureat reflux under N2
  2. concentrationThe mixture was concentrated
  3. additiona saturated aqueous solution of NaHCO3 (500 mL) was carefully added
  4. stirringThe mixture was stirred for 30 minutes
  5. customuntil bubbling
  6. customThe biphase was separated
  7. extractionthe aqueous was re-extracted with CH2Cl2 (500 mL)
  8. dry with materialThe combined organic phases were dried (Na2SO4)
  9. filtrationfiltered
  10. concentrationconcentrated
  11. customto obtain a brown oil, which
  12. customcrystallized
  13. custom7-Chlorothieno[3,2-b]pyridine has also been prepared

Sources & evidence

ORD record
ord-dad6d4800bdd4237a8d34a5549fb1f51
Source dataset
uspto-grants-2011_08
Patent number
US08003662B2

Reaction notes

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