Trifluoroacetic acid → HCID 22860941, compound

HRID 399547Notes

Reaction equation

HRID 399547 reaction equation
[CH2:1]([O:8][C:9](=[O:34])[C@H:10]([CH2:27][C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1)[NH:11][C:12](=[O:26])[C@H:13]([CH2:22][CH:23]([CH3:25])[CH3:24])[NH:14][C:15](OC(C)(C)C)=[O:16])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.FC(F)(F)C(O)=O.[C:42]([NH:49][C@H:50](C(O)=O)[CH:51]([CH3:53])[CH3:52])([O:44][C:45]([CH3:48])([CH3:47])[CH3:46])=[O:43].C1C=CC2N(O)N=NC=2C=1.C1CCC(N=C=NC2CCCCC2)CC1>C1COCC1.C(Cl)Cl>[CH2:1]([O:8][C:9](=[O:34])[C@H:10]([CH2:27][C:28]1[CH:29]=[CH:30][CH:31]=[CH:32][CH:33]=1)[NH:11][C:12](=[O:26])[C@H:13]([CH2:22][CH:23]([CH3:25])[CH3:24])[NH:14][C:15](=[O:16])[C@H:50]([CH:51]([CH3:53])[CH3:52])[NH:49][C:42]([O:44][C:45]([CH3:47])([CH3:46])[CH3:48])=[O:43])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

8

Reactant 5

HCID 6422Trifluoroacetic acidHCID 10868DicyclohexylcarbodiimideHCID 757711-HydroxybenzotriazoleHCID 83693Boc-L-ValineHCID 15138263HCID 15138263, compound

Product 1

HCID 22860941HCID 22860941, compoundYield 75%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

A 500 mL round bottom flask was charged with 46.52 g (99 mmol) N-tert-Butyloxycarbonyl-L-leucinyl-L-phenylalanine benzyl ester, 340 mL anhydrous methylene chloride (CH2Cl2), and 51 mL trifluoroacetic acid (TFA). The mixture was stirred at room temperature under a nitrogen atmosphere for 3 hours, and then concentrated in vacuo. The residue was azetroped twice with toluene, and carried on. The same 500 mL round bottom flask containing the crude TFA salt was placed under a nitrogen atmosphere and charged with 21.5 g (99 mmol) Boc-L-valine, 13.4 g (99 mmol) HOBT, and 270 mL anhydrous THF. The solution was cooled in an ice/acetone bath and 21.4 g (104 mmol) DCC was added in one portion. The mixture was stirred in the cold for 1 hour, and then warmed to room temperature and stirred overnight. The precipitated DCU was filtered off, and the filtrate was concentrated in vacuo. The residue was taken up in ethyl acetate and washed once with water, once with a 10% solution of citric acid, once with saturated NaHCO3, and once with brine. The organic layer was then dried over Na2SO4, filtered, and concentrated in vacuo. The resultant solid was precipitated from ethanol with H2O to provide 41.96 g (75%) of the title compound.

Workup

  1. concentrationconcentrated in vacuo
  2. additionThe same 500 mL round bottom flask containing the crude TFA salt
  3. temperatureThe solution was cooled in an ice/acetone bath
  4. stirringThe mixture was stirred in the cold for 1 hour
  5. temperaturewarmed to room temperature
  6. stirringstirred overnight
  7. filtrationThe precipitated DCU was filtered off
  8. concentrationthe filtrate was concentrated in vacuo
  9. washwashed once with water, once with a 10% solution of citric acid, once with saturated NaHCO3
  10. dry with materialThe organic layer was then dried over Na2SO4
  11. filtrationfiltered
  12. concentrationconcentrated in vacuo
  13. customThe resultant solid was precipitated from ethanol with H2O

Sources & evidence

ORD record
ord-48f6dc51bebb42fa8d3b73154b1cc8fb
Source dataset
uspto-grants-1998_10
Patent number
US05821331

Reaction notes

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