Dicyclohexylcarbodiimide → HCID 11826518, compound

HRID 1277355Notes

Reaction equation

HRID 1277355 reaction equation
[NH:1]1[CH2:15][CH2:14][CH2:13][C@H:2]1[C:3]([O:5][CH2:6][C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1)=[O:4].Cl.[NH:17]([C:29]([O:31][C:32]([CH3:35])([CH3:34])[CH3:33])=[O:30])[C@H:18]([C:26](O)=[O:27])[CH2:19][C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1.C1CCC(N=C=NC2CCCCC2)CC1>C(Cl)(Cl)Cl.C(O)(=O)C.C1COCC1.C(N(CC)CC)C>[NH:17]([C:29]([O:31][C:32]([CH3:35])([CH3:34])[CH3:33])=[O:30])[C@H:18]([C:26]([N:1]1[CH2:15][CH2:14][CH2:13][C@H:2]1[C:3]([O:5][CH2:6][C:7]1[CH:8]=[CH:9][CH:10]=[CH:11][CH:12]=1)=[O:4])=[O:27])[CH2:19][C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1

Participants

8

Reactant 3

HCID 10868DicyclohexylcarbodiimideHCID 77857L-Phenylalanine, N-[(1,1-dimethylethoxy)carbonyl]-HCID 2733413Proline benzyl ester hydrochloride

Product 1

HCID 11826518HCID 11826518, compoundYield 75.1%

Reagents, catalysts & solvents 4

HCID 176Acetic AcidSolventHCID 6212ChloroformSolvent2×HCID 8028TetrahydrofuranSolvent2×HCID 8471TriethylamineSolvent

Procedure

To 121 g of H-Pro-OBzl·HCl, 400 ml of THF was added and 70 ml of triethylamine was added dropwise thereto under cooling with stirring. Further, 100 ml of THF and 50 ml of chloroform were added thereto. To the resultant mixture, 132 g of BOC-Phe-OH was added and 113 g of DCC dissolved in 100 ml of chloroform was added dropwise under cooling with stirring over a period of 1 hour. The mixture was stirred at a temperaturebelow 10° C. and after 16 hours, 5 ml of acetic acid was added thereto under cooling. After stirring for an additional 2 hours, the insoluble materials were removed by filtration and the filtrate was washedwith THF and concentrated in vacuo. The resultant oily residue was dissolved in 1 liter of ethyl acetate and the insoluble materials were removed by filtration. The filtrate was washed with water, 1 N hydrochloric acid, water, a 5% sodium bicarbonate aqueous solution and water, dried over magnesium sulfate and concentrated in vacuo. The resultant oily residue was dissolved in diethyl ether and crystallized by addition of n-hexane. The crystals were recrystallized from ethyl acetate-n-hexane to obtain 169 g (yield: 74.8%) of the desired material having a melting point of 104°-106° C.

Workup

  1. temperatureunder cooling
  2. additionwas added dropwise
  3. temperatureunder cooling
  4. stirringwith stirring over a period of 1 hour
  5. stirringThe mixture was stirred at a temperaturebelow 10° C. and after 16 hours
  6. temperatureunder cooling
  7. stirringAfter stirring for an additional 2 hours
  8. customthe insoluble materials were removed by filtration
  9. concentrationconcentrated in vacuo
  10. dissolutionThe resultant oily residue was dissolved in 1 liter of ethyl acetate
  11. customthe insoluble materials were removed by filtration
  12. washThe filtrate was washed with water, 1 N hydrochloric acid, water
  13. dry with materiala 5% sodium bicarbonate aqueous solution and water, dried over magnesium sulfate
  14. concentrationconcentrated in vacuo
  15. dissolutionThe resultant oily residue was dissolved in diethyl ether
  16. customcrystallized by addition of n-hexane
  17. customThe crystals were recrystallized from ethyl acetate-n-hexane

Sources & evidence

ORD record
ord-725fba9f9b0e4159b65d08efcae43e41
Source dataset
uspto-grants-1981_07
Patent number
US04277393

Reaction notes

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