1,8-Diazabicyclo(5.4.0)undec-7-ene → HCID 17947306, compound

HRID 392914Notes

Reaction equation

HRID 392914 reaction equation
[H-].[Al+3].[Li+].[H-].[H-].[H-].C(O[C:15](=O)[C:16]1[CH:21]=[C:20]([C:22]#[CH:23])[CH:19]=[CH:18][C:17]=1[O:24][CH2:25][C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1)C1C=CC=CC=1.C(OC1C=CC(C#C)=CC=1CO)C1C=CC=CC=1.C(OC1C=CC(C=C)=CC=1CO)C1C=CC=CC=1.C1CCN2C(=NCCC2)CC1.C1(P([N:94]=[N+:95]=[N-:96])(C2C=CC=CC=2)=O)C=CC=CC=1>C1COCC1.C1(C)C=CC=CC=1.O>[CH2:25]([O:24][C:17]1[CH:18]=[CH:19][C:20]([CH:22]=[CH2:23])=[CH:21][C:16]=1[CH2:15][N:94]=[N+:95]=[N-:96])[C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1

Participants

10

Reactant 6

HCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 199401P,P-Diphenylphosphinic azideHCID 21226445Aluminium lithium hydrideHCID 69706309HCID 69706309, compoundHCID 86594478HCID 86594478, compoundHCID 86594479HCID 86594479, compound

Product 1

HCID 17947306HCID 17947306, compoundYield 39%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 1140TolueneSolventHCID 8028TetrahydrofuranSolvent

Procedure

Lithium aluminum hydride (95 mg, 2.49 mmol) was added to a solution of 2-benzyloxy-5-ethynyl-benzoic acid benzyl ester (680 mg, 1.99 mmol) in THF (5 mL) at 0° C. After 15 minutes, the reaction was quenched by the sequential addition of water (100 μL), 15% NaOH (100 μL), and water (300 μL). The mixture was diluted with ethyl acetate (10 mL) and dried (MgSO4), filtered, and concentrated. The residue was purified by flash chromatography (10% ethyl acetate/hexanes) to afford 600 mg of a ˜1:1 mixture of 2-benzyloxy-5-ethynyl-benzyl alcohol and 2-benzyloxy-5-ethenyl-benzyl alcohol. This mixture was dissolved in toluene (8 mL) and treated with DBU (0.7 mL, 4.52 mmol) and diphenyl phosphoryl azide (1.1 mL, 5.12 mmol) at room temperature. After 18 hours, water was added and the mixture was extracted with ethyl acetate (3×). The combined organic layers were washed with 1N HCl (1×), brine (1×), dried (Na2SO4), filtered and concentrated in vacuo. The residue was purified by flash chromatography (3.5% THF/hexanes) and the mixed fractions were rechromatographed with 3% ether/pet ether to afford 206 mg of 2-benzyloxy-5-ethenyl-benzyl azide as the faster eluting fraction. MS 238 (M−N2)+. 1H NMR (400 MHz, CDCl3) δ 7.4 (m, 7H); 6.95 (d, 1H, J=9.1 Hz); 6.62 (dd, 1H, J=17.5, 10.5 Hz); 5.61 (d, 1H, J=17.5 Hz); 5.15 (m, 3H); 4.40 (s, 2H).

Workup

  1. customthe reaction was quenched by the sequential addition of water (100 μL), 15% NaOH (100 μL), and water (300 μL)
  2. additionThe mixture was diluted with ethyl acetate (10 mL)
  3. dry with materialdried (MgSO4)
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe residue was purified by flash chromatography (10% ethyl acetate/hexanes)
  7. customto afford
  8. waitAfter 18 hours
  9. extractionthe mixture was extracted with ethyl acetate (3×)
  10. washThe combined organic layers were washed with 1N HCl (1×), brine (1×)
  11. dry with materialdried (Na2SO4)
  12. filtrationfiltered
  13. concentrationconcentrated in vacuo
  14. customThe residue was purified by flash chromatography (3.5% THF/hexanes)
  15. customthe mixed fractions were rechromatographed with 3% ether/pet ether

Sources & evidence

ORD record
ord-2269548df07e4a3b898c939f06a5b33c
Source dataset
uspto-grants-2004_10
Patent number
US06803457B1

Reaction notes

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