Acetaldehyde → 2-(3,4-Difluorophenyl)-3-methyl-3-hydroxypropionic acid

HRID 2269212Notes

Reaction equation

HRID 2269212 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([C@H:9]2[C@H:13]([CH3:14])[O:12]C(=O)N2)[CH:5]=[CH:6][C:7]=1[F:8].FC1C=C(C[C:25]([OH:27])=[O:26])C=CC=1F.[Li+].CC([N-]C(C)C)C.C(=O)C>>[F:1][C:2]1[CH:3]=[C:4]([CH:9]([CH:13]([CH3:14])[OH:12])[C:25]([OH:27])=[O:26])[CH:5]=[CH:6][C:7]=1[F:8]

Participants

5

Reactant 4

HCID 177AcetaldehydeHCID 69571(3,4-Difluorophenyl)acetic acidHCID 2724682Lithium diisopropylamideHCID 105127504(S)-(3,4-difluorophenyl)-5(S)-methyloxazolidin-2-one

Product 1

HCID 114813332-(3,4-Difluorophenyl)-3-methyl-3-hydroxypropionic acid

Procedure

4(S)-(3,4-difluorophenyl)-5(S)-methyloxazolidin-2-one precursor to Compound A can be prepared by treating 3,4-difluorophenylacetic acid with LDA, followed by reaction with acetaldehyde to form 2-(3,4-difluorophenyl)-3-methyl-3-hydroxypropionic acid, and then cyclizing the hydroxypropionic acid with diphenyldiphosphorylazide to form the oxazolidinone. The oxazolidinone can then be activated by treatment with p-nitrophenylchloroformate. The oxazolidinones can be resolved into their optical isomers via chromatography prior to activation, or the unresolved material can be activated directly. The activated oxazolidinone is then acylated to give Compound A by treatment with 3-[4-(4-fluorophenyl)piperidin-1-yl]propylamine.

Workup

  1. customcan be prepared

Sources & evidence

ORD record
ord-87a5df08da08400ea63eb766a28cd78a
Source dataset
uspto-grants-2001_12
Patent number
US06329393B1

Reaction notes

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