Benzyl Alcohol → 4-Benzyloxy-N-(4-fluorobenzyl)-5-methoxy-6-methylnicotinamide

HRID 1931221Notes

Reaction equation

HRID 1931221 reaction equation
[F:1][C:2]1[CH:21]=[CH:20][C:5]([CH2:6][NH:7][C:8](=[O:19])[C:9]2[C:14]([OH:15])=[C:13]([O:16][CH3:17])[C:12]([CH3:18])=[N:11][CH:10]=2)=[CH:4][CH:3]=1.[CH2:22](O)[C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1.C(P(CCCC)CCCC)CCC.N(C(OC(C)C)=O)=NC(OC(C)C)=O.C1(C)C=CC=CC=1>O1CCCC1>[CH2:22]([O:15][C:14]1[C:9]([C:8]([NH:7][CH2:6][C:5]2[CH:4]=[CH:3][C:2]([F:1])=[CH:21][CH:20]=2)=[O:19])=[CH:10][N:11]=[C:12]([CH3:18])[C:13]=1[O:16][CH3:17])[C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1

Participants

6

Reactant 4

HCID 244Benzyl AlcoholHCID 13831TributylphosphineHCID 66880968DIAD tolueneHCID 178493183HCID 178493183, compound

Product 1

HCID 577224874-Benzyloxy-N-(4-fluorobenzyl)-5-methoxy-6-methylnicotinamideYield 52.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of the compound 22 (100 g, 344 mmol), benzyl alcohol (46 ml, 447 mmol), and tributylphosphine (128 ml, 516 mmol) in tetrahydrofuran (1000 ml) was added a 40% diisopropyl azodicarboxylate-toluene solution (280 ml, 516 mmol) under ice-cooling over 30 minutes. After stirred for 30 minutes under ice-cooling, a temperature was raised to room temperature, followed by stirring for 2 hours. The solvent was distilled off under reduced pressure, to the residue were added toluene (100 ml) and hexane (2000 ml), and precipitated crystals were filtered. The solvent was distilled off under reduced pressure, to the residue were added diethyl ether (200 ml) and hexane (2000 ml), and precipitated crystals were filtered. The solvent was distilled off under reduced pressure, and the residue was purified by silica gel column chromatography (hexane/ethyl acetate). 4-Benzyloxy-N-(4-fluorobenzyl)-5-methoxy-6-methylnicotinamide 23 (68.5 g, 52%) was obtained as a colorless crystal.

Workup

  1. temperaturecooling over 30 minutes
  2. temperaturecooling
  3. stirringby stirring for 2 hours
  4. distillationThe solvent was distilled off under reduced pressure, to the residue
  5. additionwere added toluene (100 ml) and hexane (2000 ml)
  6. customprecipitated crystals
  7. filtrationwere filtered
  8. distillationThe solvent was distilled off under reduced pressure, to the residue
  9. additionwere added diethyl ether (200 ml) and hexane (2000 ml)
  10. customprecipitated crystals
  11. filtrationwere filtered
  12. distillationThe solvent was distilled off under reduced pressure
  13. customthe residue was purified by silica gel column chromatography (hexane/ethyl acetate)

Sources & evidence

ORD record
ord-6248058d7536495a98569328e8b3e74e
Source dataset
uspto-grants-2012_05
Patent number
US08188271B2

Reaction notes

Loading…