1,2-Dichloroethane → (R)-2-((S)-2-benzyloxycarbonylamino-3-hydroxy-propionylamino)-propionic acid methyl ester

HRID 1475274Notes

Reaction equation

HRID 1475274 reaction equation
C(N(C(C)C)CC)(C)C.Cl.[CH3:11][O:12][C:13](=[O:17])[C@H:14]([NH2:16])[CH3:15].C(Cl)CCl.[C:22]([NH:32][C@H:33]([C:36](O)=[O:37])[CH2:34][OH:35])([O:24][CH2:25][C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1)=[O:23]>C(Cl)Cl>[CH3:11][O:12][C:13](=[O:17])[C@H:14]([NH:16][C:34](=[O:35])[C@@H:33]([NH:32][C:22]([O:24][CH2:25][C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1)=[O:23])[CH2:36][OH:37])[CH3:15]

Participants

6

Reactant 4

HCID 111,2-DichloroethaneHCID 81531DiisopropylethylamineHCID 100310N-(Benzyloxycarbonyl)-L-serineHCID 11182647Methyl D-alaninate hydrochloride

Product 1

HCID 70981817(R)-2-((S)-2-benzyloxycarbonylamino-3-hydroxy-propionylamino)-propionic acid methyl esterYield 74.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Diisopropylethylamine (375 mL) was added dropwise to a cooled mixture of (R)-2-amino-propionic acid methyl ester hydrochloride (100 g, 0.716 mol), EDC (165 g, 0.86 mol), carbobenzyloxy-L-serine (171.4 g, 0.716 mol) and DCM (3.6 L). The resulting mixture was stirred under nitrogen at ambient temperature for 16 h. After removing solvent in vacuo at 40° C., the residue was diluted with saturated sodium carbonate (1 L), water (1 L) and extracted with EtOAc (2 L, 2×1 L). The combined organic phases were washed with 2 M hydrochloric acid (1 L), saturated brine solution (1 L), dried over magnesium sulfate and concentrated in vacuo at 40° C., to give the title compound (172 g) as a colourless solid. 1H NMR (Me-d3-OD): 7.44-7.28 (6H, m), 5.13 (2H, s), 4.46 (1H, d), 4.43 (1H, d), 4.25 (1H, t), 3.82-3.68 (5H, m), 1.39 (3H, d).

Workup

  1. customAfter removing solvent in vacuo at 40° C.
  2. additionthe residue was diluted with saturated sodium carbonate (1 L), water (1 L)
  3. extractionextracted with EtOAc (2 L, 2×1 L)
  4. washThe combined organic phases were washed with 2 M hydrochloric acid (1 L), saturated brine solution (1 L)
  5. dry with materialdried over magnesium sulfate
  6. concentrationconcentrated in vacuo at 40° C.

Sources & evidence

ORD record
ord-e52d151d048e43f5b0756527b4ca59e5
Source dataset
uspto-grants-2015_04
Patent number
US09018214B2

Reaction notes

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