Triethylamine → N-carbobenzoxy-L-alanyl-N-cyclopentylglycine ethyl ester

HRID 2418184Notes

Reaction equation

HRID 2418184 reaction equation
[C:1]([NH:11][C@H:12]([C:14]([OH:16])=O)[CH3:13])([O:3][CH2:4][C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1)=[O:2].C(N(CC)CC)C.C(Cl)(=O)OCC(C)C.Cl.[CH2:33]([O:35][C:36](=[O:44])[CH2:37][NH:38][CH:39]1[CH2:43][CH2:42][CH2:41][CH2:40]1)[CH3:34]>O1CCCC1.C(Cl)(Cl)Cl>[CH2:33]([O:35][C:36](=[O:44])[CH2:37][N:38]([C:14](=[O:16])[C@H:12]([CH3:13])[NH:11][C:1]([O:3][CH2:4][C:5]1[CH:6]=[CH:7][CH:8]=[CH:9][CH:10]=1)=[O:2])[CH:39]1[CH2:43][CH2:42][CH2:41][CH2:40]1)[CH3:34]

Participants

7

Reactant 4

HCID 8471Triethylamine2×HCID 62365Isobutyl chloroformateHCID 736104N-carbobenzyloxyalanineHCID 13089663N-Cyclopentyl-amino-acetic acid ethyl ester hydrochloride

Product 1

HCID 13089665N-carbobenzoxy-L-alanyl-N-cyclopentylglycine ethyl esterYield 60.7%

Reagents, catalysts & solvents 2

HCID 6212ChloroformSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-10 °C

Procedure

N-Carbobenzoxy-L-alanine (11.4 g) and triethylamine (6.7 ml) are dissolved in 100 ml of tetrahydrofuran and under stirring at -10° C., 6.5 ml of isobutyl chlorocarbonate is added in small portions. Then, at -10° C. to -5° C., a solution of N-cyclopentylglycine ethyl ester hydrochloride (10 g) and triethylamine (6.7 ml) in chloroform (100 ml) is added and the mixture is allowed to stand at room temperature overnight. The reaction mixture is filtered and the filtrate is concentrated. To the residue is added 300 ml of water, followed by extraction with 200 ml of ethyl acetate. The ethyl acetate layer is washed with 5% hydrochloric acid, aqueous sodium hydrogen carbonate and water in that order and dried over sodium sulfate. Removal of the solvent by distillation gives an oil, which is separated and purified by column chromatography using 150 g of silica gel. The fractions eluted with toluene-ethyl acetate (5:1) are collected to give 11 g of N-carbobenzoxy-L-alanyl-N-cyclopentylglycine ethyl ester as an oil. This product (10 g) is dissolved in 100 ml of ethanol, then 16 ml of 2N sodium hydroxide is added, and the mixture is stirred at room temperature for 5 hours. The reaction mixture is concentrated and the concentrate is diluted with 100 ml of water and acidified with 10% hydrochloric acid, whereupon an oil separates out. This oil is extracted with 300 ml of ethyl acetate and the extract is washed with water, dried and concentrated to give 8 g of N-carbobenzoxy-L-alanyl-N-cyclopentylglycine as colorless oil.

Workup

  1. filtrationThe reaction mixture is filtered
  2. concentrationthe filtrate is concentrated
  3. additionTo the residue is added 300 ml of water
  4. extractionfollowed by extraction with 200 ml of ethyl acetate
  5. washThe ethyl acetate layer is washed with 5% hydrochloric acid, aqueous sodium hydrogen carbonate and water in that order
  6. dry with materialdried over sodium sulfate
  7. customRemoval of the solvent
  8. distillationby distillation
  9. customgives an oil, which
  10. customis separated
  11. custompurified by column chromatography
  12. washThe fractions eluted with toluene-ethyl acetate (5:1)
  13. customare collected

Sources & evidence

ORD record
ord-f9fd9ade40394cb89789fc59f60ee15e
Source dataset
uspto-grants-1984_09
Patent number
US04472383

Reaction notes

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