o-Toluenesulfonyl chloride → (S)-4-(1-azido-ethyl)-pyridine

HRID 2251844Notes

Reaction equation

HRID 2251844 reaction equation
[N:1]1[CH:6]=[CH:5][C:4]([C@H:7](O)[CH3:8])=[CH:3][CH:2]=1.[Li]CCCC.C1(C)C(S(Cl)(=O)=O)=CC=CC=1.[N-:26]=[N+:27]=[N-:28].[Na+]>C1COCC1.O>[N:26]([C@H:7]([C:4]1[CH:5]=[CH:6][N:1]=[CH:2][CH:3]=1)[CH3:8])=[N+:27]=[N-:28]

Participants

7

Reactant 4

HCID 8623o-Toluenesulfonyl chlorideHCID 33557Sodium AzideHCID 11804747(1R)-1-(pyridin-4-yl)ethan-1-olHCID 178418339Butyllithium

Product 1

HCID 10749335(S)-4-(1-azido-ethyl)-pyridine

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

(R)-1-Pyridin-4-yl-ethanol (0.160 g) was dissolved in THF (10 mL) and cooled to 0° C. nBuLi (2.5 M in hexanes, 0.52 mL) was added slowly and the reaction was stirred at 0° C. for 5 min. Toluenesulfonyl chloride (0.250 g) was added and the stirring was continued for 30 min. NaN3 (0.30 g) was added, the reaction was warmed to RT and stirred overnight. The mixture was added to H2O and the layers were separated. The aqueous layer was extracted with Et2O and the combined organic phases were dried over Na2SO4, filtered and evaporated in vacuo to yield a yellow oil. This crude material was purified by silica gel chromatography (30 g, 33 to 75% Et2O/hexanes w/1% Et3N) to afford (S)-4-(1-azido-ethyl)-pyridine as a clear oil.

Workup

  1. additionwas added slowly
  2. waitthe stirring was continued for 30 min
  3. temperaturethe reaction was warmed to RT
  4. stirringstirred overnight
  5. customthe layers were separated
  6. extractionThe aqueous layer was extracted with Et2O
  7. dry with materialthe combined organic phases were dried over Na2SO4
  8. filtrationfiltered
  9. customevaporated in vacuo
  10. customto yield a yellow oil
  11. customThis crude material was purified by silica gel chromatography (30 g, 33 to 75% Et2O/hexanes w/1% Et3N)

Sources & evidence

ORD record
ord-1e631d53475943b8ae8dfa1a2c10c46a
Source dataset
uspto-grants-2008_01
Patent number
US07320992B2

Reaction notes

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