tert-Butyl hydroperoxide → Ac-Tyr(PO3H2)-Val-Ala-N(C6H13)2

HRID 368966Notes

Reaction equation

HRID 368966 reaction equation
[NH:1]([C:45]([CH3:47])=[O:46])[C@H:2]([C:18]([NH:20][C@H:21]([C:25]([NH:27][C@H:28]([C:30]([N:32]([CH2:39][CH2:40][CH2:41][CH2:42][CH2:43][CH3:44])[CH2:33][CH2:34][CH2:35][CH2:36][CH2:37][CH3:38])=[O:31])[CH3:29])=[O:26])[CH:22]([CH3:24])[CH3:23])=[O:19])[CH2:3][C:4]1[CH:9]=[CH:8][C:7]([O:10]CC2C=CC=CC=2)=[CH:6][CH:5]=1.[H][H].N1C=NN=N1.C(N(CC)[P:58]([O:64]C(C)(C)C)[O:59]C(C)(C)C)C.C([O:75]O)(C)(C)C>[Pd].CO.C(Cl)Cl>[NH:1]([C:45]([CH3:47])=[O:46])[C@H:2]([C:18]([NH:20][C@H:21]([C:25]([NH:27][C@H:28]([C:30]([N:32]([CH2:39][CH2:40][CH2:41][CH2:42][CH2:43][CH3:44])[CH2:33][CH2:34][CH2:35][CH2:36][CH2:37][CH3:38])=[O:31])[CH3:29])=[O:26])[CH:22]([CH3:24])[CH3:23])=[O:19])[CH2:3][C:4]1[CH:9]=[CH:8][C:7]([O:10][P:58]([OH:64])([OH:75])=[O:59])=[CH:6][CH:5]=1

Participants

9

Reactant 5

HCID 6410tert-Butyl hydroperoxideHCID 4251849Di-tert-butyl diethylphosphoramiditeHCID 10604288Ac-Tyr(Bzl)-Val-Ala-N(C6H13)2HCID 178418361HCID 178418361, compoundHCID 178418441HCID 178418441, compound

Product 1

HCID 10699325Ac-Tyr(PO3H2)-Val-Ala-N(C6H13)2

Reagents, catalysts & solvents 3

HCID 23938PalladiumCatalystHCID 887MethanolSolventHCID 6344DichloromethaneSolvent

Procedure

The title compound was prepared by starting with 200 mg of Ac-Tyr(Bzl)-Val-Ala-N(C6H13)2 which was reduced with hydrogen under high pressure with 20% Pd/C catalyst in methanol. The catalyst was filtered. The solution was concentrated under reduced pressure, dissolved, and lyophilized (15B mg). The peptide was phosphotitylated with 1H-tetrazole (79.0 mg, 4.0 eq.) and di-t-butyl diethylphosphoramidite (312 mL, 4.0 eq.) in DCM (50 mL) while stirring at room temperature for 1 hour. The compound was then treated with 2.0 mL 70% aqueous t-butyl-hydroperoxide to the solution for 1 hour. The solution was then concentrated under reduced pressure. The peptide was deprotected with 95% TFA/5% water (20 mL) while stirring for 1 hour. The solution was then concentrated under reduced pressure and purified by preparative RP-HPLC using a gradient of 20% to 50% B over 120 minutes. The appropriate fractions were combined and lyophilized yielding Ac-Tyr(PO3H2)-Val-Ala-N(C6H13)2 (11.0 mg, MS=639.3, Calculated=640.43).

Workup

  1. filtrationThe catalyst was filtered
  2. concentrationThe solution was concentrated under reduced pressure
  3. dissolutiondissolved
  4. concentrationThe solution was then concentrated under reduced pressure
  5. stirringwhile stirring for 1 hour
  6. concentrationThe solution was then concentrated under reduced pressure
  7. custompurified by preparative RP-HPLC
  8. customover 120 minutes

Sources & evidence

ORD record
ord-97043420fc3f465d8b80f747bfa03e6b
Source dataset
uspto-grants-2000_10
Patent number
US06136798

Reaction notes

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