Pyruvic Acid → HCID 12083934, compound

HRID 2243832Notes

Reaction equation

HRID 2243832 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.C[N:18]1[CH2:23][CH2:22]OCC1.C1C=CC2N([OH:33])N=NC=2C=1.[C:34]([OH:39])(=O)[C:35]([CH3:37])=O.C1CCC(N=C=NC2CCCCC2)CC1>CN(C=O)C.C(Cl)Cl>[NH:18]1[C:23](=[O:33])[CH2:22][CH2:37][C@H:35]1[C:34]([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:39]

Participants

8

Reactant 5

HCID 1060Pyruvic AcidHCID 79724-MethylmorpholineHCID 10868DicyclohexylcarbodiimideHCID 757711-HydroxybenzotriazoleHCID 2733413Proline benzyl ester hydrochloride

Product 1

HCID 12083934HCID 12083934, compoundYield 69.3%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent2×

Conditions

Temperature
0 °C

Procedure

To a solution of H-Pro-OBn.HCl (10.0 g, 41.3 mmol) in anh DMF (50 mL) at 0° C. under Ar, NMM (4.55 mL, 43.8 mmol) was added dropwise by syringe while maintaining the temperature at 0° C. HOBt (18.98 g, 124 mmol) was then added in portions. After 15 min, pyruvic acid (8.61 g, 97.79 mmol) dissolved in anh DCM (10 mL) was added dropwise by syringe while maintaining the temperature below 3° C. Finally, DCC (22.17 g, 107.46 mmol) dissolved in DCM (80 mL) was added dropwise with a compensated funnel. The mixture was allowed to reach room temperature (2 h) and stirred for another 12 h. The reaction mixture was filtered to remove the precipitate and the solution was concentrated under reduced pressure. The residue was dissolved in EtOAc (500 mL) and washed successively with aq. KHSO4 (100 mL, 10%), aq. NaHCO3 (400 mL, sat.), brine (400 mL), dried (Na2SO4) and filtered. The solvent was eliminated under reduced pressure and the residue was chased with ACN (100 mL), cooled at −30° C. for 2 h and filtered to removed the excess of N,N-dicyclohexylurea. The resulting brown oil (15.82 g) was purified by flash LC (silica gel, grad. hex to hex:EtOAc 2:1) to afford F2 (9.06 g, 66% yield) as a white solid. Rf=0.25 (hex:EtOAc 2:1).

Workup

  1. additionwas added dropwise by syringe
  2. temperaturewhile maintaining the temperature below 3° C
  3. additionwas added dropwise with a compensated funnel
  4. customto reach room temperature
  5. custom(2 h)
  6. filtrationThe reaction mixture was filtered
  7. customto remove the precipitate
  8. concentrationthe solution was concentrated under reduced pressure
  9. dissolutionThe residue was dissolved in EtOAc (500 mL)
  10. washwashed successively with aq. KHSO4 (100 mL, 10%), aq. NaHCO3 (400 mL, sat.), brine (400 mL)
  11. dry with materialdried (Na2SO4)
  12. filtrationfiltered
  13. temperaturecooled at −30° C. for 2 h
  14. filtrationfiltered
  15. customto removed the excess of N,N-dicyclohexylurea
  16. customThe resulting brown oil (15.82 g) was purified by flash LC (silica gel, grad. hex to hex:EtOAc 2:1)

Sources & evidence

ORD record
ord-272d0bd94c6a47cf9b553149ce7a8c73
Source dataset
uspto-grants-2010_03
Patent number
US07678765B2

Reaction notes

Loading…