Triethylamine → HCID 178440693, compound

HRID 1424150Notes

Reaction equation

HRID 1424150 reaction equation
[C:1]([C:5]1[CH:10]=[CH:9][C:8]([NH2:11])=[C:7]([NH2:12])[CH:6]=1)([CH3:4])([CH3:3])[CH3:2].C([NH:20][C@H:21]([C:26](O)=O)[C:22]([OH:25])([CH3:24])[CH3:23])(OC(C)(C)C)=O.C(N(CC)CC)C.C(P1(=O)OP(CCC)(=O)OP(CCC)(=O)O1)CC>O1CCOCC1.CCOC(C)=O>[NH2:20][C@H:21]([C:26]1[NH:11][C:8]2[CH:9]=[CH:10][C:5]([C:1]([CH3:4])([CH3:2])[CH3:3])=[CH:6][C:7]=2[N:12]=1)[C:22]([CH3:24])([OH:25])[CH3:23]

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 111923Propylphosphonic anhydrideHCID 4327084-Tert-butylbenzene-1,2-diamineHCID 11075314N-(tert-Butoxycarbonyl)-3-hydroxy-L-valine

Product 1

HCID 178440693HCID 178440693, compoundYield 2%

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Procedure

A solution of 4-tert-butyl-1,2-diaminobenzene (1 g, 6 mmol), N-boc-3-hydroxy-L-valine (1.4 g, 6 mmol) and triethylamine (1.5 mL, 15.1 mmol) in dioxane (50 mL) was stirred at 0° C. for 15 minutes. T3P (50% w/w in EtOAc, 4.6 mL, 7.3 mmol) was added dropwise and the reaction continued stirring at this temperature for 30 minutes. The reaction was then heated to reflux for 5 hours before cooling and diluting with EtOAc. The solution was washed with saturated aqueous sodium carbonate solution twice, dried over Na2SO4 and concentrated in vacuo. The residue was purified using silica gel column chromatography eluting with 0-50% EtOAc in heptanes. The residue was dissolved in dioxane (10 mL) at 0° C. and treated with 4M HCl in dioxane (10 mL). The reaction was stirred at room temperature for 2 hours before concentrating in vacuo. The residue was washed with EtOAc and pentane before basifying with saturated aqueous NaOH solution and extracting into EtOAc. The organic layer was collected, dried over Na2SO4, concentrated in vacuo and triturated with 10% EtOH in pentane (5 mL) to afford the title compound (25 mg, 2%).

Workup

  1. temperatureThe reaction was then heated
  2. temperatureto reflux for 5 hours
  3. temperaturebefore cooling
  4. washThe solution was washed with saturated aqueous sodium carbonate solution twice
  5. dry with materialdried over Na2SO4
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified
  8. washeluting with 0-50% EtOAc in heptanes
  9. dissolutionThe residue was dissolved in dioxane (10 mL) at 0° C.
  10. additiontreated with 4M HCl in dioxane (10 mL)
  11. stirringThe reaction was stirred at room temperature for 2 hours
  12. concentrationbefore concentrating in vacuo
  13. washThe residue was washed with EtOAc and pentane
  14. extractionextracting into EtOAc
  15. customThe organic layer was collected
  16. dry with materialdried over Na2SO4
  17. concentrationconcentrated in vacuo
  18. customtriturated with 10% EtOH in pentane (5 mL)

Sources & evidence

ORD record
ord-fdc140fb1ac94a14a0c7b2d85d3edc57
Source dataset
uspto-grants-2015_01
Patent number
US08927587B2

Reaction notes

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