Ammonium Chloride → 6-(2-methoxypyrid-5-yl)-2-(1H)-quinolone

HRID 985991Notes

Reaction equation

HRID 985991 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5]([O:8][CH3:9])=[N:6][CH:7]=1.C([Li])(C)(C)C.I[C:16]1[CH:17]=[C:18]2[C:23](=[CH:24][CH:25]=1)[NH:22][C:21](=[O:26])[CH:20]=[CH:19]2.[Cl-].[NH4+].[Na+].[Na+].C(N(CC(O)=O)CC(O)=O)CN(CC([O-])=O)CC([O-])=O>O1CCCC1.CCCCC.O.[Cl-].[Zn+2].[Cl-].CO.C(Cl)(Cl)Cl>[CH3:9][O:8][C:5]1[CH:4]=[CH:3][C:2]([C:16]2[CH:17]=[C:18]3[C:23](=[CH:24][CH:25]=2)[NH:22][C:21](=[O:26])[CH:20]=[CH:19]3)=[CH:7][N:6]=1

Participants

12

Reactant 5

HCID 25517Ammonium ChlorideHCID 27348955-Bromo-2-methoxypyridineHCID 13020083Ethylenediaminetetraacetic acid disodium saltHCID 138361846-Iodoquinolin-2(1H)-oneHCID 178418306HCID 178418306, compound

Product 1

HCID 138361906-(2-methoxypyrid-5-yl)-2-(1H)-quinolone

Reagents, catalysts & solvents 6

HCID 3007855ZincchlorideCatalystHCID 887MethanolSolventHCID 962WaterSolventHCID 6212ChloroformSolventHCID 8003PentaneSolventHCID 8028TetrahydrofuranSolvent3×

Procedure

A solution of 5-bromo-2-methoxypyridine (1.50 g) in tetrahydrofuran (THF) (10 cm3) was stirred at -70° under nitrogen during the addition of t-butyllithium (8.0 cm3 of a 2.0M solution in pentane). After 10 minutes a solution of anhydrous zinc chloride (1.09 g) in tetrahydrofuran (THF) (10 cm3) was added and the mixture was allowed to warm to room temperature over 1 hour. A suspension of 6-iodo-2-(1H)-quinolone (0.813 g) and tetrakis (triphenylphosphine) palladium(O) (0.03 g) in THF (10 cm3) was then added and the mixture was heated under reflux for 3 hours. Saturated ammonium chloride solution (1 cm3) was added to the cooled mixture followed by a solution of ethylenediaminetetraacetic acid disodium salt (6.0 g) in water (100 cm3). Chloroform (100 cm3) and methanol (30 cm3) were added and the mixture was warmed until all the solid material dissolved. The phases were separated, the aqueous layer was further extracted with chloroform:methanol 9:1 (3×50 cm3), and the combined and dried (MgSO4) extracts were concentrated in vacuo to afford a solid which was recrystallised from isopropanol to give 6-(2-methoxypyrid-5-yl)-2-(1H)-quinolone, m.p. 248°-252°, (0.56 g).

Workup

  1. additionwas then added
  2. temperaturethe mixture was heated
  3. temperatureunder reflux for 3 hours
  4. temperaturethe mixture was warmed until all the solid material
  5. dissolutiondissolved
  6. customThe phases were separated
  7. extractionthe aqueous layer was further extracted with chloroform:methanol 9:1 (3×50 cm3)
  8. dry with materialdried (MgSO4) extracts
  9. concentrationwere concentrated in vacuo
  10. customto afford a solid which
  11. customwas recrystallised from isopropanol

Sources & evidence

ORD record
ord-d29d0c1739bd4c3aa47026f322aea51f
Source dataset
uspto-grants-1987_12
Patent number
US04710507

Reaction notes

Loading…