1,2-Dichloroethane → 3(S)-ethyl-prolyl-methionine isopropyl ester

HRID 1779504Notes

Reaction equation

HRID 1779504 reaction equation
[CH2:1]([C@H:3]1[CH2:7][CH2:6][NH:5][C@@H:4]1[C:8]([OH:10])=O)[CH3:2].Cl.[CH:12]([O:15][C:16](=[O:23])[C@H:17]([CH2:19][CH2:20][S:21][CH3:22])[NH2:18])([CH3:14])[CH3:13].C1C=CC2N(O)N=NC=2C=1.C(Cl)CCl.CN1CCOCC1>CN(C=O)C>[CH:12]([O:15][C:16](=[O:23])[C@H:17]([CH2:19][CH2:20][S:21][CH3:22])[NH:18][C:8](=[O:10])[C@@H:4]1[C@@H:3]([CH2:1][CH3:2])[CH2:7][CH2:6][NH:5]1)([CH3:14])[CH3:13]

Participants

7

Reactant 5

HCID 111,2-DichloroethaneHCID 79724-MethylmorpholineHCID 757711-HydroxybenzotriazoleHCID 21156159Isopropyl L-methionate hydrochlorideHCID 54352229trans-3-Ethylproline

Product 1

HCID 867507903(S)-ethyl-prolyl-methionine isopropyl ester

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

N-(t-Butyloxycarbonyl)-pyrrolidin-2(S)-ylmethyl]3(S)-ethyl-proline (2.4 g, 0.008 mol), methionine isopropyl ester hydrochloride (2.21 g, 0.0097 mol), HOBT (1.49 g, 0.0097 mol) and EDC (1.86 g, 0.0097 mol) were dissolved in DMF (15 mL) at room temperature and treated with N-methylmorpholine (3 mL, 0.024 mol). The reaction mixture was stirred overnight at room temperature, then concentrated and partitioned between EtOAc and H2O. The organic layer was washed with aq satd NaHCO3 solution, brine, and dried (MgSO4). The crude product was chromatographed on a flash silica gel column eluting with hexane: EtOAc, 7:3 to give N-(t butyloxycarbonyl)-pyrrolidin-2(S)-ylmethyl]3(S)-ethyl-prolyl-methionine isopropyl ester.

Workup

  1. concentrationconcentrated
  2. custompartitioned between EtOAc and H2O
  3. washThe organic layer was washed with aq satd NaHCO3 solution, brine
  4. dry with materialdried (MgSO4)
  5. customThe crude product was chromatographed on a flash silica gel column
  6. washeluting with hexane

Sources & evidence

ORD record
ord-7e3975dcc4c141a8aab7c62a53161b8c
Source dataset
uspto-grants-1997_05
Patent number
US05627202

Reaction notes

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