Triethylamine → 2-[(1-Tert-butoxycarbonylamino-cyclopentanecarbonyl)-amino]-3-(4-hydroxy-phenyl)-propionic acid ethyl ester

HRID 2230233Notes

Reaction equation

HRID 2230233 reaction equation
Cl.[CH2:2]([O:4][C:5](=[O:16])[C@H:6]([CH2:8][C:9]1[CH:14]=[CH:13][C:12]([OH:15])=[CH:11][CH:10]=1)[NH2:7])[CH3:3].[C:17]([NH:24][C:25]1([C:30](O)=[O:31])[CH2:29][CH2:28][CH2:27][CH2:26]1)([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18].C1C=CC2N(O)N=NC=2C=1.C1CCC(N=C=NC2CCCCC2)CC1.CCN(CC)CC>C(Cl)Cl>[CH2:2]([O:4][C:5](=[O:16])[CH:6]([NH:7][C:30]([C:25]1([NH:24][C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[CH2:29][CH2:28][CH2:27][CH2:26]1)=[O:31])[CH2:8][C:9]1[CH:10]=[CH:11][C:12]([OH:15])=[CH:13][CH:14]=1)[CH3:3]

Participants

7

Reactant 5

HCID 8471TriethylamineHCID 10868DicyclohexylcarbodiimideHCID 757711-HydroxybenzotriazoleHCID 2724939Tyrosine ethyl ester hydrochlorideHCID 27346451-tert-Butoxycarbonylaminocyclopentanecarboxylic acid

Product 1

HCID 700271362-[(1-Tert-butoxycarbonylamino-cyclopentanecarbonyl)-amino]-3-(4-hydroxy-phenyl)-propionic acid ethyl ester

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

3.0 g (12.2 mmol) of tyrosine ethyl ester hydrochloride and 2.8 g (12.2 mmol) of N-Boc-cycloleucine are suspended in 10 mL of CH2Cl2. 1.65 g (12.2 mmol) of HOBT, 3.02 g (14.6 mmol) of DCC, and 1.7 mL (12.2 mmol) of Et3N are added, and the solution is stirred at room temperature overnight. The reaction mixture is filtered, and CH2Cl2 is removed in vacuo. The residue is taken up in EtOAc, filtered, and washed successively with 1N HCl, water, saturated aqueous NaHCO3 solution, and brine, then dried over MgSO4, filtered, and concentrated. The residue is purified by chromatography on silica gel (50% EtOAc/hexane) to yield 2-[(1-tert-butoxycarbonylamino-cyclopentanecarbonyl)-amino]-3-(4-hydroxy-phenyl)-propionic acid ethyl ester; 1H NMR (250 MHz, CDCl3) δ7.97 (d, 2 H), 6.7 (d, 2 H), 7.51 (d, 1 H), 5.58 (s, 1 H), 4.70-4.80 (m, 2 H), 4.12 (q, 2 H), 3.02 (d, 2 H), 2.07-2.35 (m, 2 H), 1.60-2.00 (m, 6 H), 1.40 (s, 9 H), 1.20 (t, 3H).

Workup

  1. filtrationThe reaction mixture is filtered
  2. customCH2Cl2 is removed in vacuo
  3. filtrationfiltered
  4. washwashed successively with 1N HCl, water, saturated aqueous NaHCO3 solution, and brine
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe residue is purified by chromatography on silica gel (50% EtOAc/hexane)

Sources & evidence

ORD record
ord-a49e71550e1046dd89b955631d952de6
Source dataset
uspto-grants-2002_07
Patent number
US06423727B1

Reaction notes

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