4-Methylmorpholine → BOC-Thr-Cys(MBzl)-Thr-ol

HRID 1903336Notes

Reaction equation

HRID 1903336 reaction equation
C(OC(Cl)=O)C(C)C.[NH:9]([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[C@H:10]([C:14]([OH:16])=O)[C@@H:11]([CH3:13])[OH:12].CN1CCOCC1.[NH2:31][C@H:32]([C:43]([NH:45][C@H:46]([CH2:50][OH:51])[C@@H:47]([CH3:49])[OH:48])=[O:44])[CH2:33][S:34][CH2:35][C:36]1[CH:42]=[CH:41][C:39]([CH3:40])=[CH:38][CH:37]=1.FC(C(O)=O)(F)F>C1COCC1>[NH:9]([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[C@H:10]([C:14]([NH:31][C@H:32]([C:43]([NH:45][C@H:46]([CH2:50][OH:51])[C@@H:47]([CH3:49])[OH:48])=[O:44])[CH2:33][S:34][CH2:35][C:36]1[CH:42]=[CH:41][C:39]([CH3:40])=[CH:38][CH:37]=1)=[O:16])[C@@H:11]([CH3:13])[OH:12]

Participants

6

Reactant 4

HCID 79724-Methylmorpholine2×HCID 62365Isobutyl chloroformateHCID 2724766N-tert-Butoxycarbonyl-L-threonineHCID 131713415H-Cys(MBzl)-Thr-ol trifluoroacetate

Product 1

HCID 131713417BOC-Thr-Cys(MBzl)-Thr-ol

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-25 °C

Procedure

5.9 ml chloroformic acid isobutyl-ester are added drop-wise to a solution of 9.7 g Boc-Thr-OH and 9.4 ml N-methyl-morpholine in 50 ml THF pre-cooled to -25° C. The solution is stirred for 5 min. at -15° C. and a solution of 20 g H-Cys(MBzl)-Thr-ol trifluoroacetate and 9.8 ml N-methylmorpholine in 50 ml THF, pre-cooled to -10° C. are added. The reaction mixture is stirred for 2 hrs. at 0° C., and for 2 hrs. at room temperature. 20 ml 10% KHCO3 are added and the mixture concentrated under vacuum. The product is diluted with AcOEt and washed with 2 N citric acid, 10% KHCO3 solution and then 30% NaCl solution. The AcOEt phase is dried over Na2SO4 and evaporated under vacuum, and the residue re-crystallised from MeOH/AcOEt/hexane. The title compound is obtained after further filtration, washing with ether and drying:

Workup

  1. additionare added
  2. stirringThe reaction mixture is stirred for 2 hrs
  3. waitat 0° C., and for 2 hrs
  4. customat room temperature
  5. concentrationthe mixture concentrated under vacuum
  6. additionThe product is diluted with AcOEt
  7. washwashed with 2 N citric acid, 10% KHCO3 solution
  8. dry with materialThe AcOEt phase is dried over Na2SO4
  9. customevaporated under vacuum
  10. customthe residue re-crystallised from MeOH/AcOEt/hexane

Sources & evidence

ORD record
ord-c9a57006f434418682ad51765a988ff4
Source dataset
uspto-grants-1984_03
Patent number
US04435385

Reaction notes

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