Trifluoroacetic acid → HCID 131712661, compound

HRID 1106300Notes

Reaction equation

HRID 1106300 reaction equation
[NH:1]([C:24]([O:26]C(C)(C)C)=O)[C@H:2]([C:7]([NH:9][C@H:10]([C:14]([O:16][CH2:17][C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1)=[O:15])[C@@H:11]([CH3:13])[OH:12])=[O:8])[CH2:3][C:4](=[O:6])[NH2:5].C(O)(C(F)(F)F)=O.[NH:38]([C:48]([O:50][C:51]([CH3:54])([CH3:53])[CH3:52])=[O:49])[C@H:39](C(O)=O)[CH2:40][CH2:41][S:42]([CH3:44])=[O:43].C1C2C3C(=O)N(O)C(=O)C3C1C=C2.C1CCC(N=C=NC2CCCCC2)CC1>C1COCC1>[NH:38]([C:48]([O:50][C:51]([CH3:54])([CH3:53])[CH3:52])=[O:49])[C@H:39]([C:24]([NH:1][C@H:2]([C:7]([NH:9][C@H:10]([C:14]([O:16][CH2:17][C:18]1[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=1)=[O:15])[C@@H:11]([CH3:13])[OH:12])=[O:8])[CH2:3][C:4](=[O:6])[NH2:5])=[O:26])[CH2:40][CH2:41][S:42]([CH3:44])=[O:43]

Participants

7

Reactant 5

HCID 6422Trifluoroacetic acidHCID 10868DicyclohexylcarbodiimideHCID 895293a,4,7,7a-Tetrahydro-2-hydroxy-4,7-methano-1H-isoindole-1,3(2H)-dioneHCID 7408090Boc-Met(O)-OhHCID 131711783HCID 131711783, compound

Product 1

HCID 131712661HCID 131712661, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To 50.0 g of Boc-Asn-Thr-OBzl is added 170 ml of TFA and the mixture is shaken at room temperature for 30 minutes. The solution is concentrated and treated with 500 ml of diethyl ether. The resultant powder is collected by filtration and dried. It is dissolved in 400 ml of THF, and under ice-cooling 20 ml of TEA is added. To this solution is added Boc-Met(O)-ONB (prepared by dissolving 31.3 g of Boc-Met(O).OH and 23.3 g of HONB in 200 ml of THF, adding 26.8 g of DCC under ice-cooling and stirring the mixture for 4 hours). The mixture is stirred for 15 hours, after which time the solvent is distilled off under reduced pressure. To the residue are added ethyl acetate (200 ml) and ether (200 ml), and the resultant powders are collected by filtration and reprecipitated from acetonitrile. Yield 48.5 g (72.0%), m.p. 145°-147° C., [α]D23 -6.5° (c=1.1, DMF), Rf1 =0.19.

Workup

  1. concentrationThe solution is concentrated
  2. additiontreated with 500 ml of diethyl ether
  3. filtrationThe resultant powder is collected by filtration
  4. customdried
  5. dissolutionIt is dissolved in 400 ml of THF
  6. temperatureunder ice-cooling 20 ml of TEA
  7. additionis added
  8. additionTo this solution is added Boc-Met(O)-ONB (
  9. customprepared
  10. temperaturecooling
  11. stirringstirring the mixture for 4 hours)
  12. stirringThe mixture is stirred for 15 hours
  13. distillationafter which time the solvent is distilled off under reduced pressure
  14. additionTo the residue are added ethyl acetate (200 ml) and ether (200 ml)
  15. filtrationthe resultant powders are collected by filtration
  16. customreprecipitated from acetonitrile

Sources & evidence

ORD record
ord-0c03792db83547caa4a55fd3570e1609
Source dataset
uspto-grants-1982_01
Patent number
US04312943

Reaction notes

Loading…