Triethylamine → N-morpholinocarbonyl-L-phenylalanine benzyl ester

HRID 1088612Notes

Reaction equation

HRID 1088612 reaction equation
C1(C)C=CC(S(O)(=O)=[O:8])=CC=1.[CH2:12]([O:19][C:20](=[O:30])[C@H:21]([CH2:23][C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1)[NH2:22])[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1.[CH2:31]([N:33]([CH2:36]C)[CH2:34]C)C.Cl[C:39]([O:41][C:42](Cl)(Cl)Cl)=O>C1(C)C=CC=CC=1>[CH2:12]([O:19][C:20](=[O:30])[C@H:21]([CH2:23][C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1)[NH:22][C:31]([N:33]1[CH2:36][CH2:42][O:41][CH2:39][CH2:34]1)=[O:8])[C:13]1[CH:14]=[CH:15][CH:16]=[CH:17][CH:18]=1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 10426DiphosgeneHCID 12636207L-phenylalanine benzyl ester p-toluenesulfonate

Product 1

HCID 14478228N-morpholinocarbonyl-L-phenylalanine benzyl ester

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
80 °C

Procedure

To a solution of L-phenylalanine benzyl ester p-toluenesulfonic acid salt (4.27 g) in dry toluene (50 ml) was added triethylamine (1.01 g) and trichloromethyl chloroformate (0.732 ml). The mixture was stirred at 80° C. for 30 minutes. After evaporation of the solvent, the residue was dissolved in dry tetrahydrofuran (40 ml) and morpholine (871 mg) was added to the solution at ambient temperature. The mixture was stirred at the same temperature for 3 hours. After evaporation of the solvent, the residue was dissolved in ethyl acetate (100 ml) and the solution was washed with 5% hydrochloric acid, saturated sodium bicarbonate solution and water successively, dried over magnesium sulfate, and concentrated under reduced pressure. The residue was purified with silica gel column chromatography (30% ethyl acetate in n-hexane as eluent) to give N-morpholinocarbonyl-L-phenylalanine benzyl ester (3.02 g) as an amorphous powder.

Workup

  1. customAfter evaporation of the solvent
  2. dissolutionthe residue was dissolved in dry tetrahydrofuran (40 ml)
  3. additionmorpholine (871 mg) was added to the solution at ambient temperature
  4. stirringThe mixture was stirred at the same temperature for 3 hours
  5. customAfter evaporation of the solvent
  6. dissolutionthe residue was dissolved in ethyl acetate (100 ml)
  7. washthe solution was washed with 5% hydrochloric acid, saturated sodium bicarbonate solution and water successively
  8. dry with materialdried over magnesium sulfate
  9. concentrationconcentrated under reduced pressure
  10. customThe residue was purified with silica gel column chromatography (30% ethyl acetate in n-hexane as eluent)

Sources & evidence

ORD record
ord-5533ea54274a4c5db05766d09d73b7ae
Source dataset
uspto-grants-1990_10
Patent number
US04963530

Reaction notes

Loading…