Triethylamine → HCID 131714253, compound

HRID 1248639Notes

Reaction equation

HRID 1248639 reaction equation
Cl.[CH3:2][O:3][C:4](=[O:10])[C@@H:5]1[CH2:9][CH2:8][CH2:7][NH:6]1.C(N(CC)CC)C.C1(N=C=NC2CCCCC2)CCCCC1.[O:33]=[C:34]1[NH:38][CH:37]([CH2:39][CH2:40][C:41](O)=[O:42])[CH2:36][CH2:35]1>ClCCl.CN(C)C1C=CN=CC=1>[O:42]=[C:41]([N:6]1[CH2:7][CH2:8][CH2:9][C@H:5]1[C:4]([O:3][CH3:2])=[O:10])[CH2:40][CH2:39][CH:37]1[CH2:36][CH2:35][C:34](=[O:33])[NH:38]1

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 10868DicyclohexylcarbodiimideHCID 2733200methyl L-prolinate hydrochlorideHCID 45856673-(5-Oxopyrrolidin-2-yl)propanoic acid

Product 1

HCID 131714253HCID 131714253, compound

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

A solution of 5.0 g (0.03 mol) L-proline methyl ester hydrochloride is dissolved in 30 ml of dichloromethane. The solution is cooled to 0° C. and 4.42 ml (0.032 mol) triethylamine is added dropwise over a ten minute period. The mixture is stirred 15 minutes and a mixture of the following is added in a single addition: 6.85 g (0.033 mol) of dicyclohexylcarbodiimide; 200 mg (0.0016 mol) of 4-dimethylaminopyridine; 4.71 g (0.03 mol) of 5-oxo-2-pyrrolidinepropanoic acid. The reaction is allowed to warm to room temperature and stirred for 24 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 12:1 dichloromethanemethanol for elution. Concentration at reduced pressure followed by heating at 0.1 mm pressure and 60° C. yields 1-[1-oxo-3-(5-oxo-2-pyrrolidinyl)propyl]-L-proline, methyl ester as an analytically pure oil (0.55 hydrate) with the following characteristic proton NMR spectrum: 1H-NMR (CDCL3) 1.6-2.5 (m, 14H), 3.4-3.85 (m, 2H), 3. (s, 3H), 4.5 (m, 1H), 6.37 (m, 1H).

Workup

  1. additiona mixture of the following
  2. additionis added in a single addition
  3. temperatureto warm to room temperature
  4. stirringstirred for 24 hours
  5. customThe solids are removed by filtration
  6. washare washed with 15 ml of 0° C. dichloromethane
  7. concentrationThe filtrate is concentrated at reduced pressure to an oil
  8. customThe oil is chromatographed over silica gel using 12:1 dichloromethanemethanol for elution
  9. concentrationConcentration at reduced pressure
  10. temperatureby heating at 0.1 mm pressure and 60° C.

Sources & evidence

ORD record
ord-98f2a641dcb149b2a3ccc89680b38497
Source dataset
uspto-grants-1985_06
Patent number
US04525476

Reaction notes

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