Methanol → (2S,3R)-methyl 2-amino-3-hydroxy-3-(4-methoxyphenyl)propanoate

HRID 58864Notes

Reaction equation

HRID 58864 reaction equation
S(Cl)(Cl)=O.[NH2:5][CH:6]([CH:10]([OH:19])[C:11]1[CH:16]=[CH:15][C:14]([O:17][CH3:18])=[CH:13][CH:12]=1)[C:7]([OH:9])=[O:8].[CH3:20]O>>[NH2:5][C@@H:6]([C@H:10]([OH:19])[C:11]1[CH:16]=[CH:15][C:14]([O:17][CH3:18])=[CH:13][CH:12]=1)[C:7]([O:9][CH3:20])=[O:8]

Participants

4

Reactant 3

HCID 887MethanolHCID 24386Thionyl ChlorideHCID 155945622-Amino-3-hydroxy-3-(4-methoxyphenyl)propanoic acid

Product 1

HCID 10632944(2S,3R)-methyl 2-amino-3-hydroxy-3-(4-methoxyphenyl)propanoateYield 59%

Procedure

Thionyl chloride (12.3 mL, 169 mmol) was added dropwise to methanol (250 mL) at 0° C. followed by addition of 2-amino-3-hydroxy-3-(4-methoxyphenyl)propanoic acid (25.0 g, 118 mol). The reaction mixture was stirred at ambient temperature for 1 h and heated under reflux for 3 h. The mixture was cooled to ambient temperature and then concentrated to dryness. The residue was purified by flash column chromatography on silica gel (DCM/methanol=60:1) to afford (2S,3R)-methyl 2-amino-3-hydroxy-3-(4-methoxyphenyl)propanoate (15.7 g, 59% yield, threo-) as a colorless oil. Further separation by chiral preparative HPLC afforded (2S,3R)-methyl 2-amino-3-hydroxy-3-(4-methoxyphenyl)propanoate (7.0 g, 45% yield).

Workup

  1. temperatureheated
  2. temperatureunder reflux for 3 h
  3. temperatureThe mixture was cooled to ambient temperature
  4. concentrationconcentrated to dryness
  5. customThe residue was purified by flash column chromatography on silica gel (DCM/methanol=60:1)

Sources & evidence

ORD record
ord-fda32a62bbcc40218992526651ec75da
Source dataset
uspto-grants-2016_09
Patent number
US09434761B2

Reaction notes

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