4-Methylmorpholine → Fmoc-Glu(OBut)-Arg(Pmc)-Val-Asp(Allyl)-OBzl

HRID 413999Notes

Reaction equation

HRID 413999 reaction equation
[NH:1]([C:15]([O:17][CH2:18][CH:19]1[C:31]2[C:26](=[CH:27][CH:28]=[CH:29][CH:30]=2)[C:25]2[C:20]1=[CH:21][CH:22]=[CH:23][CH:24]=2)=[O:16])[C@H:2](C(O)=O)[CH2:3][CH2:4][C:5](=[O:11])[O:6][C:7]([CH3:10])([CH3:9])[CH3:8].C1CN([P+](ON2N=NC3C=CC=CC2=3)(N2CCCC2)N2CCCC2)CC1.F[P-](F)(F)(F)(F)F.CN1CC[O:69][CH2:68]C1.[NH2:72][C@H:73]([C:99]([NH:101][C@H:102]([C:106]([NH:108][C@H:109]([C:117]([O:119][CH2:120][C:121]1[CH:126]=[CH:125][CH:124]=[CH:123][CH:122]=1)=[O:118])[CH2:110][C:111](=[O:116])[O:112][CH2:113][CH:114]=[CH2:115])=[O:107])[CH:103]([CH3:105])[CH3:104])=[O:100])[CH2:74][CH2:75][CH2:76][NH:77][C:78](=[NH:98])[NH:79][S:80]([C:83]1[C:96]([CH3:97])=[C:94]([CH3:95])[C:93]2[O:92][C:89]([CH3:91])([CH3:90])[CH2:88][CH2:87][C:86]=2[C:84]=1[CH3:85])(=[O:82])=[O:81]>C(#N)C>[NH:1]([C:15]([O:17][CH2:18][CH:19]1[C:20]2[C:25](=[CH:24][CH:23]=[CH:22][CH:21]=2)[C:26]2[C:31]1=[CH:30][CH:29]=[CH:28][CH:27]=2)=[O:16])[C@H:2]([C:68]([NH:72][C@H:73]([C:99]([NH:101][C@H:102]([C:106]([NH:108][C@H:109]([C:117]([O:119][CH2:120][C:121]1[CH:126]=[CH:125][CH:124]=[CH:123][CH:122]=1)=[O:118])[CH2:110][C:111](=[O:116])[O:112][CH2:113][CH:114]=[CH2:115])=[O:107])[CH:103]([CH3:104])[CH3:105])=[O:100])[CH2:74][CH2:75][CH2:76][NH:77][C:78](=[NH:98])[NH:79][S:80]([C:83]1[C:96]([CH3:97])=[C:94]([CH3:95])[C:93]2[O:92][C:89]([CH3:90])([CH3:91])[CH2:88][CH2:87][C:86]=2[C:84]=1[CH3:85])(=[O:82])=[O:81])=[O:69])[CH2:3][CH2:4][C:5](=[O:11])[O:6][C:7]([CH3:9])([CH3:8])[CH3:10]

Participants

6

Reactant 4

HCID 79724-Methylmorpholine2×HCID 2724637Fmoc-L-glutamic acid 5-tert-butyl esterHCID 2724699PyBOPHCID 178459571Arg(Pmc)-Val-Asp(OAllyl)-OBzl

Product 1

HCID 178459568Fmoc-Glu(OBut)-Arg(Pmc)-Val-Asp(Allyl)-OBzlYield 57.3%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent2×

Conditions

Temperature
3 °C

Procedure

To a solution of Fmoc-Glu(tBu) (6.73 g, 15.8 mmol) and benzotriazolyloxy-tris[pyrrolidino]-phosphonium hexafluoroacetate (PyBOP, 8.18 g, 15.8 mmol) in 105 mL acetonitrile at 2° C. is added N-methylmorpholine (1.58 g, 15.8 mmol) and the reaction mixture is stirred at 2-4° C. for 30 minutes. A solution of L)Arg(Pmc)-Val-Asp(OAllyl)-OBzl (12.4 g, 15.8 mmole) in 70 mL acetonitrile is added at 2° .C over 20 minutes. N-methylmorpholine is then added to achieve pH 7. Cooling is ceased, and the mixture is allowed to warm to ambient temperature, then stirred is continued for a total of 3 hours. The milky reaction mixture is filtered (slow) and the white residue is dried in the filter overnight to afford 10.8 g of Fmoc-Glu(OBut)-Arg(Pmc)-Val-Asp(Allyl)-OBzl. The filtrate is concentrated to give a gum, which is taken up in 30 mL acetonitrile and allowed to stand for 48 hours, producing an additional 3.45 g of product. The total yield of Fmoc-Glu(OtBu)-Arg(Pmc)-Val-Asp(OAllyl)-OBzl is 14.3 g. (Mcalc 1192; M+1obsvd 1192.4)

Workup

  1. temperatureCooling
  2. temperatureto warm to ambient temperature
  3. stirringstirred
  4. customis continued for a total of 3 hours
  5. customThe milky reaction mixture
  6. filtrationis filtered (slow)
  7. customthe white residue is dried in the filter overnight

Sources & evidence

ORD record
ord-44b0dfbe93f94f4ab6371d908662da81
Source dataset
uspto-grants-2003_05
Patent number
US06569993B1

Reaction notes

Loading…