Triethylamine → HCID 13473137, compound

HRID 1248636Notes

Reaction equation

HRID 1248636 reaction equation
Cl.[CH3:2][O:3][C:4](=[O:11])[C@H:5]([CH2:7][CH:8]([CH3:10])[CH3:9])[NH2:6].C(N(CC)CC)C.C1(N=C=NC2CCCCC2)CCCCC1.[O:34]=[C:35]1[NH:39][CH:38]([CH2:40][CH2:41][C:42](O)=[O:43])[CH2:37][CH2:36]1>ClCCl.CN(C)C1C=CN=CC=1>[O:43]=[C:42]([NH:6][C@H:5]([C:4]([O:3][CH3:2])=[O:11])[CH2:7][CH:8]([CH3:10])[CH3:9])[CH2:41][CH2:40][CH:38]1[CH2:37][CH2:36][C:35](=[O:34])[NH:39]1

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 10868DicyclohexylcarbodiimideHCID 2723695Leucine methyl ester hydrochlorideHCID 45856673-(5-Oxopyrrolidin-2-yl)propanoic acid

Product 1

HCID 13473137HCID 13473137, compound

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

A solution of 3.0 g (0.017 mol) L-Leucine methyl ester hydrochloride is dissolved in 30 ml of dichloromethane. The solution is cooled to 0° C. and 4.05 ml (0.029 mol) of triethylamine is added dropwise over a ten minute period. The mixture is stirred ten minutes, filtered and concentrated at reduced pressure. The oil is dissolved in 17 ml of dichloromethane and the following is added in a single addition: 4.35 g (0.021 mol) of dicyclohexylcarbodiimide; 100 mg (0.0008 mol) of 4-dimethylaminopyridine; 2.66 g (0.017 mol) of 5-oxo-2-pyrrolidinepropanoic acid. The reaction is allowed to warm to room temperature and stirred for 20 hours. The solids are removed by filtration and are washed with 15 ml of 0° C. dichloromethane. The filtrate is concentrated at reduced pressure to an oil. The oil is chromatographed over silica gel using 93:7 dichloromethanemethanol for elution. Concentration at reduced pressure followed by heating at 0.1 mm pressure and 50 ° C. yields crystalline analytically pure (as a 0.33 hydrate) N-[1-oxo-3-(5-oxo-2-pyrrolidinyl) propyl]-L-leucine, methyl ester with a melting point of 70°-74.5° C.

Workup

  1. filtrationfiltered
  2. concentrationconcentrated at reduced pressure
  3. dissolutionThe oil is dissolved in 17 ml of dichloromethane
  4. additionthe following is added in a single addition
  5. temperatureto warm to room temperature
  6. stirringstirred for 20 hours
  7. customThe solids are removed by filtration
  8. washare washed with 15 ml of 0° C. dichloromethane
  9. concentrationThe filtrate is concentrated at reduced pressure to an oil
  10. customThe oil is chromatographed over silica gel using 93:7 dichloromethanemethanol for elution
  11. concentrationConcentration at reduced pressure
  12. temperatureby heating at 0.1 mm pressure and 50 ° C.

Sources & evidence

ORD record
ord-79f7bf7ddffc479ab13f2ec967ff97d7
Source dataset
uspto-grants-1985_06
Patent number
US04525476

Reaction notes

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