Benzyl Alcohol → 6-Benzyloxy-3-fluoro-2-methoxy-pyridine

HRID 451248Notes

Reaction equation

HRID 451248 reaction equation
[CH2:1]([OH:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[H-].[Na+].[F:11][C:12]1[C:13]([O:19][CH3:20])=[N:14][C:15](F)=[CH:16][CH:17]=1>C1COCC1.O>[CH2:1]([O:8][C:15]1[N:14]=[C:13]([O:19][CH3:20])[C:12]([F:11])=[CH:17][CH:16]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

6

Reactant 3

HCID 244Benzyl AlcoholHCID 24758Sodium hydrideHCID 669368673,6-Difluoro-2-methoxypyridine

Product 1

HCID 671272546-Benzyloxy-3-fluoro-2-methoxy-pyridineYield 41.6%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

step 2—To a solution of benzyl alcohol (1.12 g, 10.3 mmol) in THF was added NaH (0.413 g, 10.3 mmol, 60% mineral oil dispersion) and stirred for 30 min. To this solution was added 140 (1.5 g, 10.3 mmol) and the resulting solution was irradiated in the microwave synthesizer at 100° C. for 1 h. The reaction was cooled, diluted with H2O, extracted with EtOAc (2×50 mL). The combined extracts were washed with brine, dried (Na2SO4), filtered and concentrated. The crude product was purified by SiO2 chromatography to afford 1 g (41%) of 6-benzyloxy-3-fluoro-2-methoxy-pyridine (142).

Workup

  1. customthe resulting solution was irradiated in the microwave synthesizer at 100° C. for 1 h
  2. temperatureThe reaction was cooled
  3. extractionextracted with EtOAc (2×50 mL)
  4. washThe combined extracts were washed with brine
  5. dry with materialdried (Na2SO4)
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe crude product was purified by SiO2 chromatography

Sources & evidence

ORD record
ord-ca5dbb5396ab4768b64fae0a117b844b
Source dataset
uspto-grants-2013_07
Patent number
US08487103B2

Reaction notes

Loading…