P,P-Diphenylphosphinic azide → 6-Amino-2-methoxy-8-methylquinoline

HRID 568382Notes

Reaction equation

HRID 568382 reaction equation
C([Li])CCC.Br[C:7]1[CH:8]=[C:9]2[C:14](=[C:15]([CH3:17])[CH:16]=1)[N:13]=[C:12]([O:18][CH3:19])[CH:11]=[CH:10]2.C1(P([N:34]=[N+]=[N-])(C2C=CC=CC=2)=O)C=CC=CC=1.[H-].COCCO[Al+]OCCOC.[Na+].[H-]>CCCCCC.O1CCCC1.C1(C)C=CC=CC=1>[NH2:34][C:7]1[CH:8]=[C:9]2[C:14](=[C:15]([CH3:17])[CH:16]=1)[N:13]=[C:12]([O:18][CH3:19])[CH:11]=[CH:10]2

Participants

8

Reactant 4

HCID 199401P,P-Diphenylphosphinic azideHCID 14220967HCID 14220967, compoundHCID 21584525Sodium bis(2-methoxyethoxy)aluminiumhydrideHCID 178418339Butyllithium

Product 1

HCID 198670716-Amino-2-methoxy-8-methylquinoline

Reagents, catalysts & solvents 3

HCID 1140TolueneSolventHCID 8028TetrahydrofuranSolvent2×HCID 8058HexaneSolvent

Procedure

n-Butyllithium (13.75 cm3 of a 1.6M solution in n-hexane) was added dropwise to a stirred solution of 6-bromo-2-methoxy-8-methylquinoline (5.04 g) in tetrahydrofuran (THF) (50 cm3) at -70° under nitrogen. After 15 minutes the fine suspension was transferred via a cannula to a stirred solution of diphenylphosphorylazide (5.5 g) in THF (50 cm3) at -70° under nitrogen. The dark solution was stirred at -70° for 2 hours, warmed to -20° over 1 hour and then re-cooled to -70°. A solution of sodium bis(2-methoxyethoxy)aluminium hydride (23.5 cm3 of a 3.4M solution in toluene) was slowly added and the solution was warmed to room temperature over 1.5 hours. The mixture was cooled to 0°, ice (100 g) was cautiously added, the resulting suspension was filtered, and the solid was washed with ethyl acetate. The aqueous filtrate was further extracted with ethyl acetate (2×100 cm3) and the combined and dried (MgSO4) organic extracts were evaporated in vacuo to give a residue which was chromatographed on silica (Merck "MK 60.9385" [Trade Mark]). Elution with toluene, followed by combination and evaporation of appropriate fractions, gave a solid which was recrystallised from hexane to afford 6-amino-2-methoxy-8-methylquinoline, m.p. 115°-117° (1.07 g).

Workup

  1. temperaturewarmed to -20° over 1 hour
  2. temperaturere-cooled to -70°
  3. temperatureThe mixture was cooled to 0°
  4. filtrationthe resulting suspension was filtered
  5. washthe solid was washed with ethyl acetate
  6. extractionThe aqueous filtrate was further extracted with ethyl acetate (2×100 cm3)
  7. dry with materialdried (MgSO4) organic extracts
  8. customwere evaporated in vacuo
  9. customto give a residue which
  10. customwas chromatographed on silica (Merck "MK 60.9385" [Trade Mark])
  11. washElution with toluene
  12. customfollowed by combination and evaporation of appropriate fractions
  13. customgave a solid which
  14. customwas recrystallised from hexane

Sources & evidence

ORD record
ord-dd275bb516204eaa84515cf0b0e3ed57
Source dataset
uspto-grants-1988_03
Patent number
US04728653

Reaction notes

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