Trifluoroacetic acid → HCID 18631442, compound

HRID 1194563Notes

Reaction equation

HRID 1194563 reaction equation
[OH:1][C@H:2]([C@@H:8]([NH:15][C:16]([O:18]C(C)(C)C)=O)[C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1)[CH2:3][C:4]([O:6][CH3:7])=[O:5].[CH:23]1[CH:24]=[CH:25][C:26]2N(O)N=[N:29][C:27]=2C=1.FC(F)(F)[C:35]([OH:37])=[O:36]>C(Cl)Cl>[C:35]([NH:29][C@H:27]([C:16]([NH:15][CH:8]([C:9]1[CH:10]=[CH:11][CH:12]=[CH:13][CH:14]=1)[CH:2]([OH:1])[CH2:3][C:4]([O:6][CH3:7])=[O:5])=[O:18])[CH2:26][CH2:25][CH2:24][CH3:23])([O:37][C:9]([CH3:14])([CH3:10])[CH3:8])=[O:36]

Participants

5

Reactant 3

HCID 6422Trifluoroacetic acidHCID 757711-HydroxybenzotriazoleHCID 13961157HCID 13961157, compound

Product 1

HCID 18631442HCID 18631442, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

In 10 ml of pure trifluoroacetic acid was dissolved at 0° C. 1 g (0.0032 mol) of methyl (3S,4S)-3-hydroxy-4-(N-BOC-amino)-4-phenylbutanoate partially in racemic form. After 15 min. at 0° C., the acid was rapidly evaporated off under reduced pressure wlthout heatlng. Then the vapor had disappeared, the salt so obtained was suspended in methylene chloride at 0° C. and therewere successively added 1.06 g (0.0032 mol) of BOC-Nle-ObSU, 0.620 g (0.004 mol) of HOBt and then a sufficient amount of NEM to bring the pH of the solution to 6-7. The reaction medium was heated to room-temperature in 2 h, while controling the pH, and then stirred for 12 to 15 h. The solvent was evaporated off at room-temperature using a Buchi evaporator and the peptide was extracted by means of ethyl acetate. The organic phase was then washed with 4 fractions of a dilute aqueous solution of sodium carbonate, 2 fractions of water, 4 fractions of a dilute aqueous solution of potassium hydrogenosulphate then with 2 fractions of water and only one fraction of an aqueous solution of sodium chloride. The medium was dried on magnesium sulphate and purified by chromatography on silicagel while eluting with a 1/1 mixture of methylene chloride/ethyl acetate. After triturating in an ethyl ether/hexane mixture, 0.629 g of methyl 4-(N-BOC-norleucylamino)-3-hydroxy-4-phenylbutanoate was obtained.

Workup

  1. customthe acid was rapidly evaporated off under reduced pressure wlthout heatlng
  2. customthe salt so obtained
  3. temperatureThe reaction medium was heated to room-temperature in 2 h
  4. customThe solvent was evaporated off at room-temperature
  5. customa Buchi evaporator
  6. extractionthe peptide was extracted by means of ethyl acetate
  7. washThe organic phase was then washed with 4 fractions of a dilute aqueous solution of sodium carbonate, 2 fractions of water, 4 fractions of a dilute aqueous solution of potassium hydrogenosulphate
  8. customThe medium was dried on magnesium sulphate
  9. custompurified by chromatography on silicagel
  10. washwhile eluting with a 1/1 mixture of methylene chloride/ethyl acetate
  11. customAfter triturating in an ethyl ether/hexane mixture

Sources & evidence

ORD record
ord-669702cac620462dbc1b06bed4e2584a
Source dataset
uspto-grants-1989_03
Patent number
US04814485

Reaction notes

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