Diethyl Ether → HCID 21464420, compound

HRID 1940923Notes

Reaction equation

HRID 1940923 reaction equation
[CH2:1]([O:3][C:4]1[CH:9]=[CH:8][N:7]=[C:6]([F:10])[CH:5]=1)[CH3:2].C([Li])CCC.CC[O:18][CH2:19]C.C1(P([N:35]=[N+]=[N-])(C2C=CC=CC=2)=O)C=CC=CC=1.[C:38]([OH:42])([CH3:41])([CH3:40])[CH3:39]>O1CCCC1.CCCCCC.ClCCl>[CH2:1]([O:3][C:4]1[CH:9]=[CH:8][N:7]=[C:6]([F:10])[C:5]=1[NH:35][C:19](=[O:18])[O:42][C:38]([CH3:41])([CH3:40])[CH3:39])[CH3:2]

Participants

9

Reactant 5

HCID 3283Diethyl EtherHCID 6386tert-ButanolHCID 199401P,P-Diphenylphosphinic azideHCID 214644144-Ethoxy-2-fluoropyridineHCID 178418339Butyllithium

Product 1

HCID 21464420HCID 21464420, compound

Reagents, catalysts & solvents 3

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolventHCID 8058HexaneSolvent

Procedure

To a solution of 18.5 g (131 mmol) of 4-ethoxy-2-fluoropyridine in 300 mL of dry tetrahydrofuran at -78° C. was added slowly, with stirring and cooling to maintain the temperature below -65° C., 58 mL of 2.5M butyl lithium in hexane. The mixture was allowed to react for 1 hr and then the resulting slurry was poured into 1300 mL of ether containing excess powdered dry ice (carbon dioxide). The fine white precipitate that formed was collected by filtration and dried under reduced pressure for 90 min. The hygroscopic solid obtained was taken into 700 mL of t-butanol and 68 g (0.24 mol) of diphenyl phosphoryl azide was added with stirring. This mixture was slowly warmed to reflux for 2 hr during which time there was a vigorous evolution of nitrogen. The resulting slurry was filtered and the filtrate was diluted with 800 mL of dichloromethane. The organic phase was separated, washed with water (2×100 mL), and concentrated by evaporation to obtain a semi-solid residue. This was dissolved in fresh dichloromethane and the solution was dried over magnesium sulfate, filtered, and concentrated by evaporation. The residue was purified by column chromatography to obtain 19.5 g (63 percent of theory) of the title compound as a colorless solid melting at 130°-131° C.

Workup

  1. temperaturecooling
  2. customto react for 1 hr
  3. customThe fine white precipitate that formed
  4. filtrationwas collected by filtration
  5. customdried under reduced pressure for 90 min
  6. customThe hygroscopic solid obtained
  7. additionwas added
  8. stirringwith stirring
  9. temperatureThis mixture was slowly warmed
  10. temperatureto reflux for 2 hr during which time there
  11. filtrationThe resulting slurry was filtered
  12. additionthe filtrate was diluted with 800 mL of dichloromethane
  13. customThe organic phase was separated
  14. washwashed with water (2×100 mL)
  15. concentrationconcentrated by evaporation
  16. customto obtain a semi-solid residue
  17. dry with materialthe solution was dried over magnesium sulfate
  18. filtrationfiltered
  19. concentrationconcentrated by evaporation
  20. customThe residue was purified by column chromatography

Sources & evidence

ORD record
ord-ff581e9595ea4f24bc7e7688cde8cf79
Source dataset
uspto-grants-1997_12
Patent number
US05700940

Reaction notes

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