Hydrochloric Acid → HCID 131711270, compound

HRID 1764777Notes

Reaction equation

HRID 1764777 reaction equation
N(C(OC(C)(C)C)=O)[C@H](C(N[C@H](C(N[C@H](C(OCC1C=CC=CC=1)=O)CC(=O)N)=O)CCC(=O)OCC1C=CC=CC=1)=O)C.Cl.[NH2:46][C@H:47]([C:49]([NH:51][C@H:52]([C:65]([NH:67][C@H:68]([C:73]([O:75][CH2:76][C:77]1[CH:82]=[CH:81][CH:80]=[CH:79][CH:78]=1)=[O:74])[CH2:69][C:70](=[O:72])[NH2:71])=[O:66])[CH2:53][CH2:54][C:55](=[O:64])[O:56][CH2:57][C:58]1[CH:63]=[CH:62][CH:61]=[CH:60][CH:59]=1)=[O:50])[CH3:48].[NH:83]([C:116]([O:118][C:119]([CH3:122])([CH3:121])[CH3:120])=[O:117])[C@H:84]([C:97]([NH:99][C@H:100]([C:113](O)=[O:114])[CH2:101][CH2:102][C:103](=[O:112])[O:104][CH2:105][C:106]1[CH:111]=[CH:110][CH:109]=[CH:108][CH:107]=1)=[O:98])[CH2:85][CH2:86][C:87](=[O:96])[O:88][CH2:89][C:90]1[CH:95]=[CH:94][CH:93]=[CH:92][CH:91]=1.ON1C(=O)CCC1=O.C1CCC(N=C=NC2CCCCC2)CC1>C1COCC1.CN(C=O)C.CCN(CC)CC>[NH:83]([C:116]([O:118][C:119]([CH3:122])([CH3:121])[CH3:120])=[O:117])[C@H:84]([C:97]([NH:99][C@H:100]([C:113]([NH:46][C@H:47]([C:49]([NH:51][C@H:52]([C:65]([NH:67][C@H:68]([C:73]([O:75][CH2:76][C:77]1[CH:78]=[CH:79][CH:80]=[CH:81][CH:82]=1)=[O:74])[CH2:69][C:70](=[O:72])[NH2:71])=[O:66])[CH2:53][CH2:54][C:55](=[O:64])[O:56][CH2:57][C:58]1[CH:63]=[CH:62][CH:61]=[CH:60][CH:59]=1)=[O:50])[CH3:48])=[O:114])[CH2:101][CH2:102][C:103](=[O:112])[O:104][CH2:105][C:106]1[CH:107]=[CH:108][CH:109]=[CH:110][CH:111]=1)=[O:98])[CH2:85][CH2:86][C:87](=[O:96])[O:88][CH2:89][C:90]1[CH:91]=[CH:92][CH:93]=[CH:94][CH:95]=1

Participants

10

Reactant 6

HCID 313Hydrochloric AcidHCID 10868DicyclohexylcarbodiimideHCID 80170N-HydroxysuccinimideHCID 13892659Boc-Glu(OBzl)-Glu(OBzl)-OHHCID 131711269HCID 131711269, compoundHCID 131711271HCID 131711271, compound

Product 1

HCID 131711270HCID 131711270, compound

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolvent2×HCID 8028TetrahydrofuranSolventHCID 8471TriethylamineSolvent2×

Procedure

Boc-Ala-Glu(OBzl)-Asn-OBzl (28.2 g; 46 mmol) was treated with 1.1 liter of 4N HCl in THF for 1 hour. Evaporation of the solvent and excess acid left an oil which was evaporated twice more with fresh THF. The residual oil turned into a solid when treated with a large volume of ether. The solid HCl.H-Ala-Glu(OBzl)-Asn-OBzl was stirred with Boc-Glu(OBzl)-Glu(OBzl)-OH (25.6 g, 46 mmol), HOSu (10.6 g, 92 mmol) and DCC (10.9 g, 53 mmol) in DMF (540 ml) at 0° for 1 hour and then at 25° for 48 hours. Et3N was added to maintain the reaction slightly basic over the entire period of time (~16 ml Et3N total). The insoluble by-products formed were filtered off and the filtrate evaporated to dryness. The crude product was dissolved in CHCl3, washed with water (3×), dried over Na2SO4 and evaporated to dryness. The product solidified when treated with petroleum ether. Recrystallized from i-PrOH: Yield, 28.9 g (59.8%); mp 169°-175°; [α]D25 =-11.78° (c 1, DMF).

Workup

  1. customEvaporation of the solvent and excess acid
  2. waitleft an oil which
  3. customwas evaporated twice more with fresh THF
  4. additiontreated with a large volume of ether
  5. temperatureto maintain
  6. customThe insoluble by-products formed
  7. filtrationwere filtered off
  8. customthe filtrate evaporated to dryness
  9. dissolutionThe crude product was dissolved in CHCl3
  10. washwashed with water (3×)
  11. dry with materialdried over Na2SO4
  12. customevaporated to dryness
  13. additiontreated with petroleum ether
  14. customRecrystallized from i-PrOH
  15. customYield

Sources & evidence

ORD record
ord-2674ebeb0a8c4be38755ce29fb23dac7
Source dataset
uspto-grants-1978_09
Patent number
US04116951

Reaction notes

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