Triethylamine → HCID 70559852, compound

HRID 443475Notes

Reaction equation

HRID 443475 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.[C:18]([O:22][C:23]([NH:25][CH2:26][C:27]([OH:29])=[O:28])=[O:24])([CH3:21])([CH3:20])[CH3:19].C1(N=C=NC2CCCCC2)CCCCC1>C(Cl)Cl.C(O)(=O)C.C(OCC)(=O)C>[C:18]([O:22][C:23]([NH:25][CH2:26][C:27]([OH:29])=[O:28])=[O:24])([CH3:21])([CH3:19])[CH3:20].[CH3:2][O:3][C:4](=[O:10])[C@@H:5]1[CH2:9][CH2:8][CH2:7][NH:6]1

Participants

8

Reactant 4

HCID 8471TriethylamineHCID 10868DicyclohexylcarbodiimideHCID 78288N-(tert-butoxycarbonyl)glycineHCID 2733200methyl L-prolinate hydrochloride

Product 1

HCID 70559852HCID 70559852, compoundYield 50%

Reagents, catalysts & solvents 3

HCID 176Acetic AcidCatalystHCID 6344DichloromethaneSolvent3×HCID 8857Ethyl AcetateSolvent

Procedure

L-proline methyl ester hydrochloride (16.6 g, 100 mmoles dissolved in 100 ml methylene chloride is treated with 14 ml (100 mmoles) of triethylamine. The precipitate which forms is removed by filtration and the filtrate is then added to 17.5 g (100 mmoles) tert-butyloxycarbonyl glycine in 150 ml methylene chloride. The resultant solution is cooled to -5° C. and 23 g (112 mmoles) of dicylohexylcarbodiimide dissolved in 25 ml of methylene chloride is added with stirring. The reaction mixture is stirred at -5° to 0° C. for approximately 90 minutes and then overnight at room temperature. A few drops of acetic acid are added to destroy excess carbodiimide and the cicyclohexyl urea precipitate is then removed from the reaction mixture by filtration. The filtrate is evaporated to afford an oily residue which is redissolved in 100 ml ethyl acetate. The resultant solution is filtered and the filtrate extracted successively with 1 M sodium carbonate/saturated sodium chloride (30:70) 1 M citric acid and saturated sodium chloride. The organic layer is separated, dried over magnesium sulfate, filtered and evaporated to afford an oil which is crystallized from ether/petroleum ether. The crystalline material is characterized using thin-layer chromatography on silica gel developed with CHCl3 /CH3OH/CH3CO2H (10:2:1). The product, tert-butyloxycarbonyl-glycine-L-proline methyl ester, obtained in 50% yield exhibits an Rf of 0.75, m.p. 66°-67° C.

Workup

  1. customThe precipitate which forms is removed by filtration
  2. additionis added
  3. stirringThe reaction mixture is stirred at -5° to 0° C. for approximately 90 minutes
  4. customovernight
  5. customat room temperature
  6. customto destroy excess carbodiimide
  7. customthe cicyclohexyl urea precipitate is then removed from the reaction mixture by filtration
  8. customThe filtrate is evaporated
  9. customto afford an oily residue which
  10. filtrationThe resultant solution is filtered
  11. extractionthe filtrate extracted successively with 1 M sodium carbonate/saturated sodium chloride (30:70) 1 M citric acid and saturated sodium chloride
  12. customThe organic layer is separated
  13. dry with materialdried over magnesium sulfate
  14. filtrationfiltered
  15. customevaporated
  16. customto afford an oil which
  17. customis crystallized from ether/petroleum ether

Sources & evidence

ORD record
ord-b07d419a91334ed09e4c7a9135fe7e56
Source dataset
uspto-grants-1981_04
Patent number
US04260681

Reaction notes

Loading…