Chloroform → cyclo-L-Ala-L-Glu(OBzl)

HRID 474177Notes

Reaction equation

HRID 474177 reaction equation
[NH:1](C(OC(C)(C)C)=O)[C@H:2]([C:4]([NH:6][C@H:7]([C:20]([O:22]C1C=CC([N+]([O-])=O)=CC=1)=O)[CH2:8][CH2:9][C:10](=[O:19])[O:11][CH2:12][C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1)=[O:5])[CH3:3].C(O)(C(F)(F)F)=O.C(Cl)(Cl)Cl.C(OC(C)=O)C>CO>[NH:1]1[C:20](=[O:22])[C@H:7]([CH2:8][CH2:9][C:10](=[O:19])[O:11][CH2:12][C:13]2[CH:14]=[CH:15][CH:16]=[CH:17][CH:18]=2)[NH:6][C:4](=[O:5])[C@@H:2]1[CH3:3]

Participants

6

Reactant 4

HCID 6212ChloroformHCID 6422Trifluoroacetic acidHCID 8857Ethyl AcetateHCID 131731165HCID 131731165, compound

Product 1

HCID 131731166cyclo-L-Ala-L-Glu(OBzl)

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
-15 °C

Procedure

Boc-L-Ala-L-Glu(OBzl)-ONp (56.0 g, 0.1 mol) was dissolved and cooled to −15° C. TFA was added and the mixture was stirred for 1 hour and gradually warmed to room temperature. Completion of the reaction was monitored by TLC using the system CHCl3:Et-OAc:MeOH=6:3:1. After completion of the reaction, the mixture was evaporated in vacuum, then twice evaporated with iso-propanol and dissolved in 500 ml of EtOAc. N-methylmorpholine was added until the mixture reached a pH level of 9 to 9.5. After 12 hours, the cyclo-L-Ala-L-Glu(OBzl) precipitated. The precipitate was filtered off, washed with EtOAc, ether and hexane. The yield was 21.0 g (70%). Rf=0.55 (CHCl3:EtOAc:MeOH:AcOH=6:3:1:0.1); HPLC data: retention time 15.9 min.

Workup

  1. temperaturegradually warmed to room temperature
  2. customAfter completion of the reaction
  3. customthe mixture was evaporated in vacuum
  4. customtwice evaporated with iso-propanol
  5. dissolutiondissolved in 500 ml of EtOAc
  6. additionN-methylmorpholine was added until the mixture
  7. waitAfter 12 hours
  8. customthe cyclo-L-Ala-L-Glu(OBzl) precipitated
  9. filtrationThe precipitate was filtered off
  10. washwashed with EtOAc, ether and hexane

Sources & evidence

ORD record
ord-60b91dcacc5844af8772311848a069d7
Source dataset
uspto-grants-2014_01
Patent number
US08637521B2

Reaction notes

Loading…