1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → Cbz-Asp(OBut)-Gly-OBn

HRID 964491

Reaction equation

HRID 964491 reaction equation
[NH:1]([C:14]([O:16][CH2:17][C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1)=[O:15])[C@H:2]([C:11]([OH:13])=O)[CH2:3][C:4](=[O:10])[O:5][C:6]([CH3:9])([CH3:8])[CH3:7].Cl.[NH2:25][CH2:26][C:27]([O:29][CH2:30][C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1)=[O:28].CCN=C=NCCCN(C)C.C1C=CC2N(O)N=NC=2C=1.CCN(C(C)C)C(C)C>ClCl.C(Cl)Cl>[NH:1]([C:14]([O:16][CH2:17][C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1)=[O:15])[C@H:2]([C:11]([NH:25][CH2:26][C:27]([O:29][CH2:30][C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1)=[O:28])=[O:13])[CH2:3][C:4](=[O:10])[O:5][C:6]([CH3:7])([CH3:8])[CH3:9]

Participants

8

Reactant 5

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 1110824-tert-Butyl hydrogen N-((phenylmethoxy)carbonyl)-L-aspartateHCID 11701227Benzyl 2-aminoacetate hydrochloride

Product 1

HCID 14375963Cbz-Asp(OBut)-Gly-OBnYield 108.9%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 24526ChlorineSolvent

Procedure

A mixture of Cbz-Asp(OBut)-OH (3590 mg, 11.1 mmol), HCl+H-Gly-OBn (3360 mg, 16.6 mmol), EDCI (3180 mg, 16.6 mmol), HOBt (2250 mg, 16.6 mmol) and DIEA (2900 mg, 16.6 mmol) in dry CH2 Cl2 (50 mL) was stirred at r.t. for six hours. The reaction mixture was added CH2Cl2 (150 mL) and washed with 1N HCl (200 mL), saturated NaHCO3 aq. (200 mL) and brine (200 mL). The organic layer was passed through an inch of SiO2 layer and the SiO2 was washed with 1/9=AcOEt/CH2Cl2 (200 mL). The eluent was evaporated in vacuo to give clear oil (5690 mg, 100%): 1H NMR (300 MHz, CDCl3) δ 7.368 (s, 10H), 7.082 (t, 1H), 6.013 (d, J=7.8 Hz, 1H), 5.164 (s, 2H), 5.126 (s, 2H), 4.592 (d, J=6.6 Hz, 1H), 4.072 (d, J=5.7 Hz, 2H), 2.891 (dd, J=18.2, 4.5 Hz, 1H), 2.641 (dd, J=17.1, 6.3 Hz, 1H), 1.423 (s, 9H); 13C NMR (300 MHz, CDCl3) δ 171.0, 170.9, 169.3, 136.1, 135.2, 129.7, 128.6 (2C), 128.4, 128.3, 128.2, 81.9, 67.3, 67.2, 51.1, 41.5, 37.3, 28.0.

Workup

  1. washwashed with 1N HCl (200 mL), saturated NaHCO3 aq. (200 mL) and brine (200 mL)
  2. washthe SiO2 was washed with 1/9=AcOEt/CH2Cl2 (200 mL)
  3. customThe eluent was evaporated in vacuo

Sources & evidence

ORD record
ord-874846bbe82a4e449dc38c8d22cfa6f1
Source dataset
uspto-grants-1998_06
Patent number
US05770380

Linked notes

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