Diisopropylamine → HCID 57577515, compound

HRID 1967307Notes

Reaction equation

HRID 1967307 reaction equation
C(N[CH:5]([CH3:7])[CH3:6])(C)C.[C:8](=[O:10])=O.[CH3:11][C:12]([CH3:14])=O.C([O:18][CH2:19][CH3:20])(=O)C.[Cl-].[NH4+:22]>O1CCCC1>[CH:12]1([C@@:8]2([OH:10])[C@H:7]([CH2:5][CH3:6])[NH:22][C:19](=[O:18])[CH2:20]2)[CH2:14][CH2:11]1

Participants

6

Reactant 4

HCID 7912DiisopropylamineHCID 8857Ethyl AcetateHCID 25517Ammonium ChlorideHCID 18522661Acetone cardice

Product 1

HCID 57577515HCID 57577515, compoundYield 39%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

A solution of diisopropylamine (7.28 g) in tetrahydrofuran (110 mL) was ice-cooled under a nitrogen atmosphere, and 1.6 mol/L n-butyllithium-hexane solution (44.1 mL) was added. The mixture was stirred at the same temperature for 20 min, and the reaction solution was cooled with dry ice/acetone. Ethyl acetate (6.96 mL) was added to the reaction solution, the mixture was stirred at the same temperature for 1 hr, and a solution of tert-butyl [(1S)-1-s (cyclopropylcarbonyl)propyl]carbamate (10.7 g) in tetrahydrofuran (60 mL) was added. The mixture was stirred at the same temperature for 5 hr, saturated aqueous ammonium chloride solution (300 mL) was added, and the mixture was extracted with ethyl acetate. The obtained organic layer was washed with saturated aqueous ammonium chloride solution and saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: ethyl acetate/hexane=5→25%), the obtained oil was dissolved in 4 mol/L hydrogen chloride-ethyl acetate solution (100 mL), and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated under reduced pressure, the residue was dissolved in tetrahydrofuran (300 mL), and diisopropylethylamine (22.7 mL) was added. The reaction solution was refluxed under heating for 4 hr, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: methanol/ethyl acetate=3→10%), and the obtained solid was recrystallized from ethyl acetate/diethyl ether/hexane to give the title compound as colorless crystals (yield: 2.80 g, 39%).

Workup

  1. temperaturecooled under a nitrogen atmosphere
  2. addition1.6 mol/L n-butyllithium-hexane solution (44.1 mL) was added
  3. stirringthe mixture was stirred at the same temperature for 1 hr
  4. stirringThe mixture was stirred at the same temperature for 5 hr
  5. extractionthe mixture was extracted with ethyl acetate
  6. washThe obtained organic layer was washed with saturated aqueous ammonium chloride solution and saturated brine
  7. dry with materialdried over anhydrous magnesium sulfate
  8. concentrationconcentrated under reduced pressure
  9. customThe residue was purified by silica gel column chromatography (eluent: ethyl acetate/hexane=5→25%)
  10. dissolutionthe obtained oil was dissolved in 4 mol/L hydrogen chloride-ethyl acetate solution (100 mL)
  11. stirringthe mixture was stirred at room temperature for 2 hr
  12. concentrationThe reaction solution was concentrated under reduced pressure
  13. dissolutionthe residue was dissolved in tetrahydrofuran (300 mL)
  14. additiondiisopropylethylamine (22.7 mL) was added
  15. temperatureThe reaction solution was refluxed
  16. temperatureunder heating for 4 hr
  17. concentrationconcentrated under reduced pressure
  18. customThe residue was purified by silica gel column chromatography (eluent: methanol/ethyl acetate=3→10%)
  19. customthe obtained solid was recrystallized from ethyl acetate/diethyl ether/hexane

Sources & evidence

ORD record
ord-08e6126df4f2419993d9e50438b48e8a
Source dataset
uspto-grants-2013_04
Patent number
US08420694B2

Reaction notes

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