1,2-Dichloroethane → 3-hydroxy-4-[N-[(phenylmethoxy)carbonyl]-L-leucyl]-1-pyrrolidinecarboxylic acid 1,1dimethylethyl ester

HRID 650470Notes

Reaction equation

HRID 650470 reaction equation
[OH:1][CH:2]1[CH:6](N)[CH2:5][N:4]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[CH2:3]1.[C:15]([NH:25][C@H:26]([C:31](O)=[O:32])[CH2:27][CH:28]([CH3:30])[CH3:29])([O:17][CH2:18][C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1)=[O:16].C1C=CC2N(O)N=NC=2C=1.C(Cl)CCl>CCOC(C)=O>[CH3:12][C:11]([O:10][C:8]([N:4]1[CH2:5][CH:6]([C:31](=[O:32])[C@H:26]([CH2:27][CH:28]([CH3:29])[CH3:30])[NH:25][C:15]([O:17][CH2:18][C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)=[O:16])[CH:2]([OH:1])[CH2:3]1)=[O:9])([CH3:14])[CH3:13]

Participants

6

Reactant 4

HCID 111,2-DichloroethaneHCID 74840Leucine, N-carboxy-, N-benzyl ester, L-HCID 757711-HydroxybenzotriazoleHCID 11229445tert-Butyl 3-amino-4-hydroxypyrrolidine-1-carboxylate

Product 1

HCID 541360223-hydroxy-4-[N-[(phenylmethoxy)carbonyl]-L-leucyl]-1-pyrrolidinecarboxylic acid 1,1dimethylethyl esterYield 65.6%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 3-hydroxy-4-amino-1-pyrrolidinecarboxylic acid, 1,1-dimethylethyl ester (202 mg, 1.14 mmol) in CH2CI2 (5 mL) was added CBZ-leucine (302.9 mg, 1.14 mmol), HOBT (154 mg, 1.14 mmol) and EDC (262.2 mg, 1.37 mmol). The reaction was allowed to stir until complete by TLC analysis whereupon it was diluted with EtOAc and washed sequentially with pH 4 buffer, sat. K2CO3, water and brine. The organic layer was dried (MgSO4), filtered and concentrated. Column chromatography of the residue (3:1 EtOAc:hexanes) gave 325 mg of the title compound: MS (ES+) 450.3 (MH+), 472.2 (M+Na).

Workup

  1. washwashed sequentially with pH 4 buffer
  2. dry with materialThe organic layer was dried (MgSO4)
  3. filtrationfiltered
  4. concentrationconcentrated

Sources & evidence

ORD record
ord-417b1d7bb7c04281b6b8e435316c9186
Source dataset
uspto-grants-2001_08
Patent number
US06274336B1

Reaction notes

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