Isoamyl Nitrite → Z-Ser-Lys(Tos)-Glu-OH

HRID 1632405Notes

Reaction equation

HRID 1632405 reaction equation
[NH:1]([C:9]([O:11][CH2:12][C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1)=[O:10])[C@H:2]([C:5]([NH:7]N)=[O:6])[CH2:3][OH:4].Cl.O1CCOCC1.N(OCCC(C)C)=O.[N-]=[N+]=[N-].N[C@H:38]([C:54]([NH:56][C@H:57]([C:63]([OH:65])=[O:64])[CH2:58][CH2:59][C:60](=[O:62])[OH:61])=[O:55])[CH2:39][CH2:40][CH2:41][CH2:42][NH:43][S:44]([C:47]1[CH:53]=[CH:52][C:50]([CH3:51])=[CH:49][CH:48]=1)(=[O:46])=[O:45]>CN(C=O)C.C(OCC)C.C(N(CC)CC)C>[NH:1]([C:9]([O:11][CH2:12][C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1)=[O:10])[C@H:2]([C:5]([NH:7][C@H:38]([C:54]([NH:56][C@H:57]([C:63]([OH:65])=[O:64])[CH2:58][CH2:59][C:60](=[O:61])[OH:62])=[O:55])[CH2:39][CH2:40][CH2:41][CH2:42][NH:43][S:44]([C:47]1[CH:53]=[CH:52][C:50]([CH3:51])=[CH:49][CH:48]=1)(=[O:46])=[O:45])=[O:6])[CH2:3][OH:4]

Participants

9

Reactant 5

HCID 8053Isoamyl NitriteHCID 33558AzideHCID 7016357(S)-Benzyl (1-hydrazinyl-3-hydroxy-1-oxopropan-2-yl)carbamateHCID 204431481,4-Dioxane hydrochlorideHCID 131713858H-Lys(Tos)-Glu-OH

Product 1

HCID 131713859Z-Ser-Lys(Tos)-Glu-OH

Reagents, catalysts & solvents 3

HCID 3283Diethyl EtherSolventHCID 6228DimethylformamideSolvent3×HCID 8471TriethylamineSolvent2×

Conditions

Temperature
-15 °C

Procedure

2.13 Grams of Z-Ser-NHNH2 was dissolved in 20 ml of DMF and 4.20 ml of 6N-hydrochloric acid/dioxane was further added, then the mixture was cooled to -15° C., 1.13 ml of isoamyl nitrite was added under stirring. After the reaction mixture shows negative reaction in hydrazid test, then a cold solution of 3.53 ml of triethylamine with 1.20 ml of DMF was added dropwise to neutralize the reaction mixture. This mixture containing the azide was added to a cold DMF solution of H-Lys(Tos)-Glu-OH obtained in above-mentioned step 2(a) with 1.96 ml of triethylamine, then this mixture was stirred at -10° to -15° C. for 2 hours and at 4° C. for 20 hours. Dimethylformamide was removed by distillation, the residue thus obtained was extracted with ethyl acetate, then the ethyl acetate layer was washed with 1N-citric acid and a saturated aqueous solution of sodium chloride, then dried with anhydrous sodium sulfate, and ethyl acetate was removed by distillation under a reduced pressure. The residue thus obtained was solidified by adding ethyl ether and reprecipitated from ethyl acetate-ether to obtain 4.14 g of the desired product.

Workup

  1. stirringthis mixture was stirred at -10° to -15° C. for 2 hours and at 4° C. for 20 hours
  2. customDimethylformamide was removed by distillation
  3. customthe residue thus obtained
  4. extractionwas extracted with ethyl acetate
  5. washthe ethyl acetate layer was washed with 1N-citric acid
  6. dry with materiala saturated aqueous solution of sodium chloride, then dried with anhydrous sodium sulfate, and ethyl acetate
  7. customwas removed by distillation under a reduced pressure
  8. customThe residue thus obtained
  9. customreprecipitated from ethyl acetate-ether

Sources & evidence

ORD record
ord-a2b6d3b339bb4e0b93ce49a75996b807
Source dataset
uspto-grants-1984_10
Patent number
US04474754

Reaction notes

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