Triphenylphosphine → 5-Bromo-2-methyl-3-nitro-6-[2,2,2-trifluoro-1-(4-fluorophenyl)ethoxy]pyridine

HRID 520263Notes

Reaction equation

HRID 520263 reaction equation
[Br:1][C:2]1[C:3]([OH:12])=[N:4][C:5]([CH3:11])=[C:6]([N+:8]([O-:10])=[O:9])[CH:7]=1.[F:13][C:14]([F:25])([F:24])[CH:15]([C:17]1[CH:22]=[CH:21][C:20]([F:23])=[CH:19][CH:18]=1)O.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[N+](C(OC(C)C)=O)(C(OC(C)C)=O)=[N-]>C1COCC1>[Br:1][C:2]1[CH:7]=[C:6]([N+:8]([O-:10])=[O:9])[C:5]([CH3:11])=[N:4][C:3]=1[O:12][CH:15]([C:17]1[CH:22]=[CH:21][C:20]([F:23])=[CH:19][CH:18]=1)[C:14]([F:13])([F:25])[F:24]

Participants

6

Reactant 4

HCID 11776TriphenylphosphineHCID 111482462,2,2-Trifluoro-1-(4-fluorophenyl)ethanolHCID 22145704Diisopropyl diazodicarboxylateHCID 178433429HCID 178433429, compound

Product 1

HCID 709800785-Bromo-2-methyl-3-nitro-6-[2,2,2-trifluoro-1-(4-fluorophenyl)ethoxy]pyridineYield 62.5%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
60 °C

Procedure

To a stirred suspension of 3-bromo-6-methyl-5-nitro-pyridin-2-ol (0.10 g, 0.43 mmol) in THF (3 mL), 2,2,2-trifluoro-1-(4-fluorophenyl)ethanol (0.13 g, 0.64 mmol, 1.5 equiv) and triphenylphosphine (0.17 g, 0.64 mmol, 1.5 eq) were added at room temperature under inert atmosphere (Ar). To this mixture, DIAD (diisopropyl diazodicarboxylate) (0.13 mL, 0.64 mmol, 1.5 eq) was added dropwise over 10 minutes while keeping the temperature below 40° C. The reaction mixture was stirred for 6 h under heating at 60° C. After this time, TLC indicted that the starting material had been consumed and the reaction mixture was allowed to reach room temperature before quenching with water (10 mL). The water phase was extracted with ethyl acetate (3×15 mL). The organic layer was washed with brine (20 mL), dried over anhydrous Na2SO4 and filtered. The solvent was removed in vacuo to give a brown residue, which was purified by combiflash column chromatography (silica gel, heptane/ethyl acetate, v/v=95/5). Fractions containing the pure compound were collected and concentrated in vacuo to give the title compound (0.11 g, 62% yield) as a yellow oil.

Workup

  1. additionwere added at room temperature under inert atmosphere (Ar)
  2. customthe temperature below 40° C
  3. customhad been consumed
  4. customto reach room temperature
  5. custombefore quenching with water (10 mL)
  6. extractionThe water phase was extracted with ethyl acetate (3×15 mL)
  7. washThe organic layer was washed with brine (20 mL)
  8. dry with materialdried over anhydrous Na2SO4
  9. filtrationfiltered
  10. customThe solvent was removed in vacuo
  11. customto give a brown residue, which
  12. customwas purified by combiflash column chromatography (silica gel, heptane/ethyl acetate, v/v=95/5)
  13. additionFractions containing the pure compound
  14. customwere collected
  15. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-b9d60355df95494290616e7fd25aa222
Source dataset
uspto-grants-2016_05
Patent number
US09326513B2

Reaction notes

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