Ammonium Chloride → (+/-)-2-Azido-6-methyl-4-(3-nitropyridin-4-yl)cyclohex-3-enol

HRID 1920222Notes

Reaction equation

HRID 1920222 reaction equation
Br[CH:2]1[CH:7](O)[CH:6]=[C:5]([C:9]2[CH:14]=[CH:13][N:12]=[CH:11][C:10]=2[N+:15]([O-:17])=[O:16])[CH2:4][CH:3]1[CH3:18].CC(C)([O-:22])C.[K+].[Cl-].[NH4+].[N-:27]=[N+:28]=[N-:29].[Na+]>C1COCC1.O>[N:27]([CH:7]1[CH:6]=[C:5]([C:9]2[CH:14]=[CH:13][N:12]=[CH:11][C:10]=2[N+:15]([O-:17])=[O:16])[CH2:4][CH:3]([CH3:18])[CH:2]1[OH:22])=[N+:28]=[N-:29]

Participants

7

Reactant 4

HCID 25517Ammonium ChlorideHCID 33557Sodium AzideHCID 23665647Potassium tert-butoxideHCID 68407746HCID 68407746, compound

Product 1

HCID 72238239(+/-)-2-Azido-6-methyl-4-(3-nitropyridin-4-yl)cyclohex-3-enolYield 55%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of (+/−)-6-bromo-5-methyl-3-(3-nitropyridin-4-yl)cyclohex-2-enol (1.0 equiv.) in THF (0.1M) was added potassium tert-butoxide (1.5 equiv.). The reaction turned from orange to black almost immediately. By TLC, the formation of product is clean in 30 min. Quenched by adding saturated ammonium chloride and ethyl acetate. The organic phase was dried with brine, then sodium sulfate, filtered, and concentrated. The crude product was dissolved in ethanol and water (3:1, 0.1M), and ammonium chloride (2.0 equiv) and sodium azide (2.0 equiv.) were added. The dark orange reaction was stirred at room temperature overnight. The conversion to product is clean as indicated by LC/MS. The reaction was concentrated to remove the ethanol, ethyl acetate and water were added, the organic phase was dried with sodium sulfate, filtered, and concentrated. The crude material was purified via silica gel column chromatography eluting with ethyl acetate and hexanes (1:1) to give (+/−)-2-azido-6-methyl-4-(3-nitropyridin-4-yl)cyclohex-3-enol in 55% yield. LC/MS=276.0 (M+H), LC=2.803 min.

Workup

  1. customQuenched
  2. additionby adding saturated ammonium chloride and ethyl acetate
  3. dry with materialThe organic phase was dried with brine
  4. filtrationsodium sulfate, filtered
  5. concentrationconcentrated
  6. dissolutionThe crude product was dissolved in ethanol
  7. customThe dark orange reaction
  8. concentrationThe reaction was concentrated
  9. customto remove the ethanol, ethyl acetate and water
  10. additionwere added
  11. dry with materialthe organic phase was dried with sodium sulfate
  12. filtrationfiltered
  13. concentrationconcentrated
  14. customThe crude material was purified via silica gel column chromatography
  15. washeluting with ethyl acetate and hexanes (1:1)

Sources & evidence

ORD record
ord-15a2dea780e640b8a9b414e127173a14
Source dataset
uspto-grants-2012_05
Patent number
US08168794B2

Reaction notes

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