Trifluoroacetic acid → HCID 67046587, compound

HRID 606566Notes

Reaction equation

HRID 606566 reaction equation
C(O[C:6]([N:8]1[CH2:12][CH:11]([F:13])[CH:10]2[O:14][CH2:15][CH:16]([OH:17])[CH:9]12)=[O:7])(C)(C)C.C(O)(C(F)(F)F)=O.CCN=C=NCCCN(C)C.Cl.C1C=CC2N(O)N=NC=2C=1.[NH:47]([C:56]([O:58][CH2:59][C:60]1[CH:65]=[CH:64][CH:63]=[CH:62][CH:61]=1)=[O:57])[C@H:48](C(O)=O)[CH2:49][CH:50]([CH3:52])[CH3:51].CCN(CC)CC.C(OC(=O)NC(C(N1CC(F)C2OCC(O)C12)=O)CC(C)C)C1C=CC=CC=1.CC(OI1(OC(C)=O)(OC(C)=O)OC(=O)C2C=CC=CC1=2)=O>C(Cl)Cl.CN(C=O)C>[CH2:59]([O:58][C:56](=[O:57])[NH:47][CH:48]([C:6]([N:8]1[CH2:12][CH:11]([F:13])[CH:10]2[O:14][CH2:15][C:16](=[O:17])[CH:9]12)=[O:7])[CH2:49][CH:50]([CH3:51])[CH3:52])[C:60]1[CH:65]=[CH:64][CH:63]=[CH:62][CH:61]=1

Participants

11

Reactant 8

HCID 6422Trifluoroacetic acidHCID 8471TriethylamineHCID 74840Leucine, N-carboxy-, N-benzyl ester, L-HCID 757711-HydroxybenzotriazoleHCID 159087TriacetoxyperiodinaneHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 67047423HCID 67047423, compoundHCID 67196853HCID 67196853, compound

Product 1

HCID 67046587HCID 67046587, compound

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent3×

Conditions

Temperature
2 °C

Procedure

6-Fluoro-3-hydroxy-hexahydro-furo[3,2-b]pyrrole-4-carboxylic acid tert-butyl ester (0.200 g, 0.81 mmol) was dissolved in DCM (4 mL) at 0° C. and TFA (4 mL) added. After stirring at 0-4° C. for 1 h, the solvent was evaporated in vacuo and the residue left under high vacuum for 4 h to afford a brown oil. The residue was dissolved in DMF (5 mL) and WSC.HCl (171 mg, 0.89 mmol), HOBt (137 mg, 1.01 mmol), Cbz-Leu-OH (226 mg, 0.85 mmol) and Et3N (337 μl, 2.43 mmol) added. After stirring at room temperature overnight, the reaction mixture was concentrated in vacuo, dissolved in EtOAc (10 mL), washed with H2O (5 mL) and saturated NaHCO3 solution (5 mL), dried (Na2SO4) and evaporated in vacuo to afford a colourless oil (242 mg; [M+H]+ 395). (1-(6-Fluoro-3-hydroxy-hexahydro-furo[3,2-b]pyrrole-4-carbonyl)-3-methyl-butyl]-carbamic acid benzyl ester (242 mg, 0.62 mmol) was dissolved in dry DCM (8 mL) and Dess-Martin periodinane (261 mg, 0.62 mmol) added. The reaction immediately turned light brown. After stirring at room temperature for 2.5 h, the yellow solution was diluted with DCM (8 mL) and washed with saturated NaHCO3 solution (5 mL), dried (Na2SO4) and evaporated in vacuo to afford a yellow residue. Purification by column chromatography (EtOAc: heptane; 1:2) yielded the title compound as a colourless oil, 147 mg; [M+H]+ 393.

Workup

  1. customthe solvent was evaporated in vacuo
  2. waitthe residue left under high vacuum for 4 h
  3. customto afford a brown oil
  4. stirringAfter stirring at room temperature overnight
  5. concentrationthe reaction mixture was concentrated in vacuo
  6. dissolutiondissolved in EtOAc (10 mL)
  7. washwashed with H2O (5 mL) and saturated NaHCO3 solution (5 mL)
  8. dry with materialdried (Na2SO4)
  9. customevaporated in vacuo
  10. customto afford a colourless oil (242 mg; [M+H]+ 395)
  11. customThe reaction immediately turned light brown
  12. stirringAfter stirring at room temperature for 2.5 h
  13. washwashed with saturated NaHCO3 solution (5 mL)
  14. dry with materialdried (Na2SO4)
  15. customevaporated in vacuo
  16. customto afford a yellow residue
  17. customPurification by column chromatography (EtOAc: heptane; 1:2)

Sources & evidence

ORD record
ord-342f230f3ebc4aaba9e1f52e2f1a1f07
Source dataset
uspto-grants-2011_03
Patent number
US07915300B2

Reaction notes

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