Methyl 2-((benzoylamino)methyl)-3-oxobutanoate → (2S,3R)-methyl-2-benzamidomethyl-3-hydroxybutyrate

HRID 1590769Notes

Reaction equation

HRID 1590769 reaction equation
[C:1]([NH:9][CH2:10][CH:11]([C:16](=[O:18])[CH3:17])[C:12]([O:14][CH3:15])=[O:13])(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1>C(Cl)Cl.[Ru]>[C:1]([NH:9][CH2:10][C@@H:11]([C@H:16]([OH:18])[CH3:17])[C:12]([O:14][CH3:15])=[O:13])(=[O:8])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

4

Reactant 1

HCID 11831808Methyl 2-((benzoylamino)methyl)-3-oxobutanoate

Product 1

HCID 10060699(2S,3R)-methyl-2-benzamidomethyl-3-hydroxybutyrateYield 90%

Reagents, catalysts & solvents 2

HCID 23950RutheniumCatalystHCID 6344DichloromethaneSolvent

Procedure

A solution was prepared by dissolving 2.5 g (10 mmol) of methyl 2-[(N-benzoylamino)methyl]-3-oxobutyrate and 84.5 mg (0.05 mmol) of the ruthenium-optically active phosphine complex prepared by following the general procedures of Referential Example 1 (Ru2Cl4 ((+)-BINAP)2 (NEt3)) in 17.5 ml of methylene chloride. The solution was placed in a 100 ml stainless steel autoclave wherein the inside air was replaced with nitrogen gas in advance. Reaction was allowed to proceed at 50° C., under a hydrogen pressure of 100 kg/cm2 for 20 hours under stirring. The solvent was distilled off and the remainder was subjected to the silica gel column chromatography (eluent; mixture of n-hexane and ethyl acetate) for removal of the catalyst to obtain 2.25 g of the title compound (yield: 90%, optical purity: 98% ee). To determine the optical purity, the compound was further derived to an ester of (+)-α-methoxy-α-trifluoromethylphenyl acetic acid, then applied to high performance liquid chromatography (column; Develosil® 100-3(4.6 mm×250 mm), manufactured by Nomura Kagaku K.K.; wave length (UV): 254 nm; eluent: hexane/diethylether=90/10; flow rate: 1 ml/min).

Workup

  1. customA solution was prepared
  2. customprepared
  3. customReaction
  4. customto proceed at 50° C., under a hydrogen
  5. customfor 20 hours
  6. distillationThe solvent was distilled off
  7. additionthe remainder was subjected to the silica gel column chromatography (eluent; mixture of n-hexane and ethyl acetate) for removal of the catalyst

Sources & evidence

ORD record
ord-1bdd90ea28e8447b88b54bffa30d2a98
Source dataset
uspto-grants-1993_04
Patent number
US05204460

Reaction notes

Loading…