Boron trifluoride etherate → 5-Acetoxy-3-ethenyl-2-fluoropyridine

HRID 2305209Notes

Reaction equation

HRID 2305209 reaction equation
N[C:2]1[CH:3]=[C:4]([CH:9]=[CH2:10])[C:5]([F:8])=[N:6][CH:7]=1.CO[CH2:13][CH2:14][O:15]C.B(F)(F)F.CC[O:23]CC.C(ON=O)(C)(C)C>CCCCC.C(Cl)Cl>[C:14]([O:15][C:2]1[CH:3]=[C:4]([CH:9]=[CH2:10])[C:5]([F:8])=[N:6][CH:7]=1)(=[O:23])[CH3:13]

Participants

7

Reactant 4

HCID 8000Boron trifluoride etherateHCID 80711,2-DimethoxyethaneHCID 10906Tert-Butyl nitriteHCID 184589355-Ethenyl-6-fluoropyridin-3-amine

Product 1

HCID 184589535-Acetoxy-3-ethenyl-2-fluoropyridineYield 40%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8003PentaneSolvent

Conditions

Temperature
0 °C

Procedure

To a stirred solution of the 5-amino-2-fluoro-3-ethenylpyridine from a above (3.00 g, 21.7 mmol) in 3:1 DME:CH2Cl2 (50 mL) at −10° C. was slowly added borontrifluoride etherate (5.60 mL, 45.6 mmol). t-Butylnitrite (3.10 mL, 26.0 mmol) was added over the course of 15 min, keeping the reaction temperature below −5° C. The reaction mixture was warmed to 0° C. and stirred for 30 min. Pentane (500 mL) was added and the solid tetrafluoroborate diazonium salt was collected by filtration. The diazonium salt was dissolved in acetic anhydride (40 mL) and heated at 95 OC for 2 h —N2 evolution was noted at 85° C. The solvent was evaporated, the residue was dissolved in Et2O (250 mL), and washed with saturated, aqueous NaHCO3 (2×150 mL). The combined aqueous phases were extracted with Et2O (2×150 mL). The combined organic phases were washed with brine (50 mL), dried (MgSO4), and concentrated. The crude product was purified by column chromatography (silica gel; EtOAc/hexane, 4:6) to afford the desired product as a yellow oil (1.51 g, 40%): 1H NMR (CDCl3, 300 MHz) δ 2.35 (s, 3H), 5.54 (d, J=11.0 Hz, 1H), 5.90 (d, J=18.0 Hz, 2H), 6.75 (m, 1H), 7.66 (dd, J=2.0, 5.0 Hz, 1H) MS (CI/NH3) m/z 182 (M+H)+, 199 (M+NH4)+.

Workup

  1. customat −10° C.
  2. customthe reaction temperature below −5° C
  3. filtrationthe solid tetrafluoroborate diazonium salt was collected by filtration
  4. dissolutionThe diazonium salt was dissolved in acetic anhydride (40 mL)
  5. temperatureheated at 95 OC for 2 h —N2 evolution
  6. customwas noted at 85° C
  7. customThe solvent was evaporated
  8. dissolutionthe residue was dissolved in Et2O (250 mL)
  9. washwashed with saturated, aqueous NaHCO3 (2×150 mL)
  10. extractionThe combined aqueous phases were extracted with Et2O (2×150 mL)
  11. washThe combined organic phases were washed with brine (50 mL)
  12. dry with materialdried (MgSO4)
  13. concentrationconcentrated
  14. customThe crude product was purified by column chromatography (silica gel; EtOAc/hexane, 4:6)

Sources & evidence

ORD record
ord-797249de2e8447c58271232b185492ab
Source dataset
uspto-grants-2002_08
Patent number
US06437138B1

Reaction notes

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