Methyl L-phenylalaninate hydrochloride → HCID 7155221, compound

HRID 1450721Notes

Reaction equation

HRID 1450721 reaction equation
N(C(OCC1C=CC=CC=1)=O)[C@H](C(O)=O)C.[NH2:17][C@H:18]([C:26]([O:28][CH3:29])=[O:27])[CH2:19][C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1.Cl.C1C=CC2N(O)N=NC=2C=1.N(C(OCC1C=CC=CC=1)=O)[C@H](C(N[C@H](C(OC)=O)CC1C=CC=CC=1)=O)C.[NH:69]([C:78]([O:80][C:81]([CH3:84])([CH3:83])[CH3:82])=[O:79])[C@H:70]([C:75](O)=[O:76])[C@H:71]([CH2:73][CH3:74])[CH3:72]>C1COCC1.CN(C=O)C>[NH:69]([C:78]([O:80][C:81]([CH3:83])([CH3:82])[CH3:84])=[O:79])[C@H:70]([C:75]([NH:17][C@H:18]([C:26]([O:28][CH3:29])=[O:27])[CH2:19][C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1)=[O:76])[C@H:71]([CH2:73][CH3:74])[CH3:72]

Participants

8

Reactant 5

HCID 75736Methyl L-phenylalaninate hydrochloride2×HCID 757711-Hydroxybenzotriazole2×HCID 736104N-carbobenzyloxyalanineHCID 2724762tert-Butoxycarbonyl-L-isoleucineHCID 6999129HCID 6999129, compound

Product 1

HCID 7155221HCID 7155221, compoundYield 85%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolvent2×HCID 8028TetrahydrofuranSolvent2×

Procedure

Having shown the removability of 1 and its derivatives from organic solvents, we next demonstrate its effectiveness as a peptide coupling reagent and general dehydrating agent. Coupling CBZ-Ala (10) and Phe-OMe.HCl in THF with HOBT and 1 afforded CBZ-Ala-Phe-OMe (21) in 84% yield. Using DMF as the solvent, the yield increased to 93%. The more hindered coupling of BOC-Ile (26) and Phe-OMe.HCl with HOBT and 1 produced yields of 82% and 85% of BOC-Ile-Phe-OMe (26) in THF and DMF, respectively. In all cases there was no racemization, as would be expected from N-carbamate-protected amino acids. The 1/HOBT mediated C-terminus coupling of CBZ-Ala-Phe (11) with Gly-OBn.TsOH in DMF produced CBZ-Ala-Phe-Gly-OBn (27) in which the Phe was racemized to the extent of 0.68% after 4 h and 1.3% after 20 h, consistent with similar experiments using DCC and EDC. The same coupling carried out in the presence of 50 mol % of anhydrous CuCl2 gave racemization-free 27, even after reactions were allowed to proceed for 20 h at room temperature. These results were also in agreement with literature data. (Miyazawa et al., Int. J. Peptide & Protein Res., 39, p. 237 (1992); Miyazawa et al., Int. J. Peptide & Protein Res., 39, p. 308 (1992).) In each case, all residual 1 and urea by-products 3 were easily removed from the reaction mixtures with a simple acid wash.

Workup

  1. customproduced

Sources & evidence

ORD record
ord-f1cfbffa332d4a87b73d32aef1c0a9bf
Source dataset
uspto-grants-1997_02
Patent number
US05602264

Reaction notes

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