Triphenylphosphine → 2-Chloro-3-[[(2S)-oxiran-2-yl]methoxy]pyridine

HRID 1483025Notes

Reaction equation

HRID 1483025 reaction equation
[O:1]1[CH2:3][C@H:2]1[CH2:4][OH:5].[Cl:6][C:7]1[C:12](O)=[CH:11][CH:10]=[CH:9][N:8]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OC(C)C)=O)=NC(OC(C)C)=O>C1COCC1>[Cl:6][C:7]1[C:12]([O:5][CH2:4][C@@H:2]2[CH2:3][O:1]2)=[CH:11][CH:10]=[CH:9][N:8]=1

Participants

6

Reactant 4

HCID 11776TriphenylphosphineHCID 75555Diisopropyl diazene-1,2-dicarboxylateHCID 811362-Chloro-3-pyridinolHCID 5460455(+)-Glycidol

Product 1

HCID 901347982-Chloro-3-[[(2S)-oxiran-2-yl]methoxy]pyridineYield 43.6%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

Combine (R)-oxiranemethanol (32.85 g, 443.5 mmol) with 2-chloro-3-hydroxypyridine (52.23 g, 403.18 mmol) in THF (1.34 L). Stir the mixture until the solids dissolve. Cool it to 0° C. and slowly add triphenylphosphine (116.33 g, 443.5 mmol). After all the solids dissolve, add diisopropyl azodicarboxylate (87.92 mL, 443.5 mmol) drop-wise over 25 minutes at a sufficiently slow rate to maintain the internal temperature of the reaction below 10° C. Stir the mixture while cooling for 30 minutes then allow the mixture to warm to ambient temperature and continue stirring overnight. Add EtOAc, and wash with NaOH (2×1.0 N). Dry the organic layer over Na2SO4; filter; and concentrate the filtrate under reduced pressure. Triturate the residue with a mixture of 2:1 Et2O: hexanes and stir for 5 minutes. Filter and concentrate the filtrate under reduced pressure to provide a residue. Purify the residue via flash column chromatography (2×330 g SiO2), eluting with a gradient of 0-66% THF/Hexane. Combine the desired fractions, and concentrate under reduced pressure to provide the title compound (32.6 g, 43.6%) as a white solid. MS (m/z): 186 (M+1).

Workup

  1. dissolutiondissolve
  2. dissolutionAfter all the solids dissolve
  3. temperatureto maintain
  4. customthe internal temperature of the reaction below 10° C
  5. stirringStir the mixture
  6. temperaturewhile cooling for 30 minutes
  7. temperatureto warm to ambient temperature
  8. stirringcontinue stirring overnight
  9. washAdd EtOAc, and wash with NaOH (2×1.0 N)
  10. dry with materialDry the organic layer over Na2SO4
  11. filtrationfilter
  12. concentrationand concentrate the filtrate under reduced pressure
  13. customTriturate the residue
  14. additionwith a mixture of 2:1 Et2O
  15. stirringhexanes and stir for 5 minutes
  16. filtrationFilter
  17. concentrationconcentrate the filtrate under reduced pressure
  18. customto provide a residue
  19. customPurify the residue via flash column chromatography (2×330 g SiO2)
  20. washeluting with a gradient of 0-66% THF/Hexane
  21. concentrationconcentrate under reduced pressure

Sources & evidence

ORD record
ord-93f32cfd125842b2bdee916822c06e39
Source dataset
uspto-grants-2016_08
Patent number
US09416138B2

Reaction notes

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