Phosphorus oxychloride → 8-Chloro-3-methoxy-1,5-naphthyridine

HRID 40259Notes

Reaction equation

HRID 40259 reaction equation
[Cl-].[Cl-].[Ca+2].[CH3:4][O:5][C:6]1[CH:15]=[C:14]2[C:9]([C:10](=O)[CH:11]=[CH:12][NH:13]2)=[N:8][CH:7]=1.O=P(Cl)(Cl)[Cl:19]>CCOC(C)=O>[Cl:19][C:10]1[CH:11]=[CH:12][N:13]=[C:14]2[C:9]=1[N:8]=[CH:7][C:6]([O:5][CH3:4])=[CH:15]2

Participants

5

Reactant 3

HCID 24813Phosphorus oxychlorideHCID 5284359Calcium ChlorideHCID 534854797-Methoxy-1,5-naphthyridin-4(1H)-one

Product 1

HCID 594273408-Chloro-3-methoxy-1,5-naphthyridine

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
120 °C

Procedure

A two-necked round bottomed flask equipped with an air condenser (protected with CaCl2 guard tube) was charged with 7-Methoxy-1H-[1,5]naphthyridin-4-one (13 g) and POCl3 (65 mL). The reaction mixture was allowed to reflux at 120° C. for 12 h. The POCl3 was removed in vacuo and azeotroped twice with toluene. EtOAc (75 mL) was added and the reaction mixture was stirred at 50-60° C. for 15-20 min. EtOAc removed separated by decantation. The organic layers were combined and concentrated. The obtained crude was dissolved in EtOAc (50 ml) and a washed with satd. aqueous sodium bicarbonate. The organic layer was dried over Na2SO4 and concentrated. The resulting solids were suspended in hexane, stirred for 15 min, filtered and dried under vacuum.

Workup

  1. customThe POCl3 was removed in vacuo
  2. customazeotroped twice with toluene
  3. additionEtOAc (75 mL) was added
  4. customEtOAc removed
  5. customseparated by decantation
  6. concentrationconcentrated
  7. customThe obtained crude
  8. washa washed with satd
  9. dry with materialThe organic layer was dried over Na2SO4
  10. concentrationconcentrated
  11. stirringstirred for 15 min
  12. filtrationfiltered
  13. customdried under vacuum

Sources & evidence

ORD record
ord-4431794d4f6d4f92a0f65b7d3c5317c1
Source dataset
uspto-grants-2013_09
Patent number
US08524900B2

Reaction notes

Loading…