Triethylamine → O-Benzyl-N-(tert-butoxycarbonyl)-L-tyrosyl-Nepsilon-benzyloxycarbonyl-L-lysine methyl ester

HRID 477714Notes

Reaction equation

HRID 477714 reaction equation
[CH3:1][O:2][C:3](=[O:28])[C@H:4]([CH2:13][CH2:14][CH2:15][CH2:16][NH:17][C:18]([O:20][CH2:21][C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1)=[O:19])[NH:5][C:6]([O:8]C(C)(C)C)=O.[CH2:29]([O:36][C:37]1[CH:55]=[CH:54][C:40]([CH2:41][C@@H:42](C(O)=O)[NH:43][C:44]([O:46][C:47]([CH3:50])([CH3:49])[CH3:48])=[O:45])=[CH:39][CH:38]=1)[C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1.C(N(CC)CC)C.C1(N=C=NC2CCCCC2)CCCCC1>FC(F)(F)C(O)=O.C(Cl)(Cl)Cl>[CH3:1][O:2][C:3](=[O:28])[C@H:4]([CH2:13][CH2:14][CH2:15][CH2:16][NH:17][C:18]([O:20][CH2:21][C:22]1[CH:23]=[CH:24][CH:25]=[CH:26][CH:27]=1)=[O:19])[NH:5][C:6](=[O:8])[C@H:42]([CH2:41][C:40]1[CH:39]=[CH:38][C:37]([O:36][CH2:29][C:30]2[CH:31]=[CH:32][CH:33]=[CH:34][CH:35]=2)=[CH:55][CH:54]=1)[NH:43][C:44]([O:46][C:47]([CH3:50])([CH3:48])[CH3:49])=[O:45]

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 10868DicyclohexylcarbodiimideHCID 98763O-benzyl-N-((tert-butoxy)carbonyl)-L-tyrosineHCID 11132998Boc-L-Lys(Z)-OMe

Product 1

HCID 15021184O-Benzyl-N-(tert-butoxycarbonyl)-L-tyrosyl-Nepsilon-benzyloxycarbonyl-L-lysine methyl esterYield 29.1%

Reagents, catalysts & solvents 2

HCID 6212ChloroformSolventHCID 6422Trifluoroacetic acidSolvent

Conditions

Temperature
0 °C

Procedure

A solution of 1.04 g (2.64 mmol) of Nε -benzyloxycarbonyl-Nα -(tert-butoxycarbonyl)-L-lysine methyl ester in 5.3 mL of trifluoroacetic acid was stirred for 2 hours at room temperature. The reaction mixture was evaporated in vacuo to give a colorless oil, which was mixed with 0.966 g (2.6 mmol) of O-benzyl-N-(tert-butoxycarbonyl)-L-tyrosine, 0.37 mL (2.6 mmol) of triethylamine and 20.8 mL of chloroform. To that mixture was added, in one portion, 0.54 g (2.6 mL) of dicyclohexylcarbodiimide at 0° C. The reaction mixture was stirred for one hour at 0° C. and then overnight at room temperature. The solvent was removed by evaporation and the residue was chromatographed on silica gel, using first methylene chloride and then 1:1 methylene chloride/ethyl acetate as eluents, to give 0.49 g (29.1%) of a colorless solid. NMR (CDCl3) δ 7.3 (10 H, m), 7.1 (2H, d), 6.85 (2H, d), 6.5 (1H, m), 5.1 (2H, s), 5.0 (1H, m), 4.7-4.1 (2H, m), 3.65 (3H, s), 3.3-2.9 (4H, m), 1.4 (9H, s). A portion of the product was recrystallized from a mixture of ethyl acetate and isopropyl ether to give crystals melting at 167°-168° C. The product has the formula ##STR118## as confirmed by elemental analysis.

Workup

  1. customThe reaction mixture was evaporated in vacuo
  2. customto give a colorless oil, which
  3. customovernight
  4. customat room temperature
  5. customThe solvent was removed by evaporation
  6. customthe residue was chromatographed on silica gel

Sources & evidence

ORD record
ord-1eaaf6d2ba014bd290b9b2c2938a22bf
Source dataset
uspto-grants-1989_12
Patent number
US04888427

Reaction notes

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