Hydrochloric Acid → (S)-2-Ethoxy-3-[2-methyl-4-(5-methyl-2-o-tolyl-oxazol-4-ylmethoxy)-phenyl]-propionic acid

HRID 1064882Notes

Reaction equation

HRID 1064882 reaction equation
C[O:2][C:3](=[O:31])[C@@H:4]([O:28][CH2:29][CH3:30])[CH2:5][C:6]1[CH:11]=[CH:10][C:9]([O:12][CH2:13][C:14]2[N:15]=[C:16]([C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][C:21]=3[CH3:26])[O:17][C:18]=2[CH3:19])=[CH:8][C:7]=1[CH3:27].[Li+].[OH-].Cl>C1COCC1.CO>[CH2:29]([O:28][C@@H:4]([CH2:5][C:6]1[CH:11]=[CH:10][C:9]([O:12][CH2:13][C:14]2[N:15]=[C:16]([C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][C:21]=3[CH3:26])[O:17][C:18]=2[CH3:19])=[CH:8][C:7]=1[CH3:27])[C:3]([OH:31])=[O:2])[CH3:30]

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 3939Lithium HydroxideHCID 69280462(S)-2-Ethoxy-3-[2-methyl-4-(5-methyl-2-o-tolyl-oxazol-4-ylmethoxy)-phenyl]-propionic acid methyl ester

Product 1

HCID 10070082(S)-2-Ethoxy-3-[2-methyl-4-(5-methyl-2-o-tolyl-oxazol-4-ylmethoxy)-phenyl]-propionic acidYield 91%

Reagents, catalysts & solvents 1

HCID 21899815MeOH tetrahydrofuranSolvent

Procedure

To a solution of (S)-2-ethoxy-3-[2-methyl-4-(5-methyl-2-o-tolyl-oxazol-4-ylmethoxy)-phenyl]-propionic acid methyl ester (100 mg, 0.24 mmol) in THF/methanol 2/1 (1.5 ml) was added a 1 N aqueous LiOH solution (1.4 ml, 1.4 mmol). The reaction mixture was stirred for 1.5 h at ambient temperature, neutralized with 1 N aqueous HCl solution under ice cooling and concentrated under reduced pressure. The residue was dissolved in 1 N HCl/ice water 1/1 and ethyl acetate, the layers were separated and the aqueous layer was extracted with ethyl acetate. The combined organic layers were washed with ice water/brine 1/1, dried over sodium sulfate and the solvent was evaporated in vacuo to give the title compound (88 mg, 0.21 mmol, 91%) as off-white solid, which was crystalized from dichloromethane/hexane to afford colorless crystals. According to chiral HPLC of the corresponding methyl ester (Chiralcel-ODH), the enantiomeric excess amounts to 98.6%.

Workup

  1. concentrationconcentrated under reduced pressure
  2. dissolutionThe residue was dissolved in 1 N HCl/ice water 1/1
  3. customethyl acetate, the layers were separated
  4. extractionthe aqueous layer was extracted with ethyl acetate
  5. washThe combined organic layers were washed with ice water/brine 1/1
  6. dry with materialdried over sodium sulfate
  7. customthe solvent was evaporated in vacuo

Sources & evidence

ORD record
ord-7497bd45e2b54245a4388a6049b1ac8f
Source dataset
uspto-grants-2005_11
Patent number
US06969725B2

Reaction notes

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