Oxalate → HCID 131717184, compound

HRID 2371373Notes

Reaction equation

HRID 2371373 reaction equation
[NH2:1][C@H:2]([C:10]([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:11])[C@@H:3]([CH3:9])[O:4][C:5]([CH3:8])([CH3:7])[CH3:6].C([O-])(=O)C([O-])=O.[K].[NH:24]([C:45]([O:47][CH2:48][C:49]1[CH:54]=[CH:53][CH:52]=[CH:51][CH:50]=1)=[O:46])[C@H:25]([C:35](ON1C(=O)CCC1=O)=[O:36])[CH2:26][CH2:27][C:28](=[O:34])[O:29][C:30]([CH3:33])([CH3:32])[CH3:31]>CCOCC.CN(C=O)C>[NH:24]([C:45]([O:47][CH2:48][C:49]1[CH:54]=[CH:53][CH:52]=[CH:51][CH:50]=1)=[O:46])[C@H:25]([C:35]([NH:1][C@H:2]([C:10]([O:12][C:13]([CH3:15])([CH3:14])[CH3:16])=[O:11])[C@@H:3]([CH3:9])[O:4][C:5]([CH3:7])([CH3:8])[CH3:6])=[O:36])[CH2:26][CH2:27][C:28](=[O:34])[O:29][C:30]([CH3:31])([CH3:33])[CH3:32]

Participants

7

Reactant 4

HCID 71081OxalateHCID 1075725-tert-Butyl 1-(2,5-dioxopyrrolidin-1-yl) (S)-2-(((phenylmethoxy)carbonyl)amino)glutarateHCID 5462222PotassiumHCID 7018832tert-Butyl O-tert-butyl-L-threoninate

Product 1

HCID 131717184HCID 131717184, compoundYield 84.2%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 6228DimethylformamideSolvent

Procedure

After suspending 3.3 g (11.0 mmol) of H-Thr(tBu)-OtBu.oxalate in 60 ml of ether, the suspension is shaken with 30 ml of 5% aqueous potassium hydrogenocarbonate solution until dissolving. The organic phase is separated, washed with an additional 20 ml of 5% aqueous potassium hydrogenocarbonate solution and then with 20 ml of water, dried over anhydrous sodium sulfate and evaporated under reduced pressure. To the solution of the oily residue in 20 ml of DMF, 4.12 g (9.5 mmol) of Z-Glu(OtBu)-OSu are added. The mixture is stirred at room temperature for 2 hours then evaporated under reduced pressure. The residue is dissolved in 50 ml of ethyl acetate and successively washed three times, three times with 15 ml of 10% aqueous citric acid solution each, twice with 15 ml of 5% aqueous sodium hydrogenocarbonate solution each, and finally with 15 ml of water, dried over anhydrous sodium sulfate and evaporated under reduced pressure. 4.4 g (8.0 mmol) of oily Z-Glu(OtBu)-Thr(tBu)-OtBu protected dipeptide (Rf1 =0.85) are obtained which is dissolved in 50 ml of methanol and hydrogenated as described in Example 1. After filtering off the catalyst, the filtrate is evaporated to yield the free H-Glu(Ot -Bu)-Thr(tBu) -OtBu dipeptide (Rf2 =0.22) which is then dissolved in 20 ml of DMF and after adding 4.77 g (10 mmol) of Z-Lys(Boc) -OSu, the reaction mixture is stirred at room temperature for 2 hours and evaporated under reduced pressure. After dissolving the oily residue in 50 ml of ethyl acetate, the solution is purified by several washings in the usual manner, dried over anhydrous sodium sulfate and evaporated under reduced pressure. The oily evaporation residue is recrystallized in ether to yield 4.75 g (74%) of Z-Lys(Boc)-Glu(OtBu)-Thr(tBu)-OtBu protected tripeptide, m.p.: 114°-115° C.; Rf2 =0.80; /α/D20 = -22.8° (c=1, methanol).

Workup

  1. dissolutionuntil dissolving
  2. customThe organic phase is separated
  3. washwashed with an additional 20 ml of 5% aqueous potassium hydrogenocarbonate solution
  4. dry with materialwith 20 ml of water, dried over anhydrous sodium sulfate
  5. customevaporated under reduced pressure
  6. customthen evaporated under reduced pressure
  7. dissolutionThe residue is dissolved in 50 ml of ethyl acetate
  8. washsuccessively washed three times, three times with 15 ml of 10% aqueous citric acid solution each, twice with 15 ml of 5% aqueous sodium hydrogenocarbonate solution each, and finally with 15 ml of water
  9. dry with materialdried over anhydrous sodium sulfate
  10. customevaporated under reduced pressure

Sources & evidence

ORD record
ord-452d58a9269141eca2a661ddf3fb72aa
Source dataset
uspto-grants-1992_03
Patent number
US05093320

Reaction notes

Loading…