Water → Tesaglitazar

HRID 1861212Notes

Reaction equation

HRID 1861212 reaction equation
[CH2:1]([O:3][C@@H:4]([CH2:10][C:11]1[CH:16]=[CH:15][C:14]([O:17][CH2:18][CH2:19][C:20]2[CH:25]=[CH:24][C:23]([O:26][S:27]([CH3:30])(=[O:29])=[O:28])=[CH:22][CH:21]=2)=[CH:13][CH:12]=1)[C:5]([O:7]CC)=[O:6])[CH3:2].C1COCC1.O.[OH-].[Li+]>CCOC(C)=O>[CH2:1]([O:3][C@@H:4]([CH2:10][C:11]1[CH:12]=[CH:13][C:14]([O:17][CH2:18][CH2:19][C:20]2[CH:21]=[CH:22][C:23]([O:26][S:27]([CH3:30])(=[O:28])=[O:29])=[CH:24][CH:25]=2)=[CH:15][CH:16]=1)[C:5]([OH:7])=[O:6])[CH3:2]

Participants

6

Reactant 4

HCID 962WaterHCID 3939Lithium HydroxideHCID 8028TetrahydrofuranHCID 11293498ethyl (S)-2-ethoxy-3-[4-[[4-(methylsulfonyloxy)phenethyl]oxy]phenyl]propanoate

Product 1

HCID 208901Tesaglitazar

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

To the oil of ethyl (S)-2-ethoxy-3-[4(2-{4-methanesulfonyloxyphenyl}ethoxy)phenyl]propanoate (723 g (71.2% assay), 1.18 mol. 1.0 eq) was added THF (3900 ml). When a homogenous solution was formed, water (900 ml) was added. The mixture was cooled to +10° C. Lithium hydroxide solution (390 ml, 4 M, 1.32 eq) was added over 1 hour. The temperature was then raised to +30° C. and the reaction allowed to proceed at this temperature for 2-3 hours. The reaction was stopped when the conversion was >99%. EtOAc (500 ml) was added and the mixture cooled to room temperature. The solution was stirred for about 30 minutes and the THF was evaporated off. When about 80-90% of the THF was evaporated, water (1900 ml) was added. The evaporation was continued until no THF remained in the mixture. The alkaline water solution was then washed with EtOAc (1000 ml, 2×1250 ml, and 950 ml). The pH of the water solution of (S)-2-ethoxy-3-[4(2-{4-methanesulfonyloxyphenyl}ethoxy)phenyl]propanoic acid was then adjusted to 2.0-2.5 with HCl (aq) (550 ml, 3.0 M). EtOAc (2500 ml) was added and the phases separated. The ethyl acetate solution of (S)-2-ethoxy-3-[4-(2-{4-methanesulfonyloxyphenyl}ethoxy)phenyl]propanoic acid was then washed with water (700 ml) and after separation evaporated to dryness. The remaining oil was then used in the following crystallisation.

Workup

  1. customWhen a homogenous solution was formed
  2. temperatureThe mixture was cooled to +10° C
  3. temperatureThe temperature was then raised to +30° C.
  4. customthe THF was evaporated off
  5. customWhen about 80-90% of the THF was evaporated
  6. additionwater (1900 ml) was added
  7. customThe evaporation
  8. washThe alkaline water solution was then washed with EtOAc (1000 ml, 2×1250 ml, and 950 ml)
  9. additionEtOAc (2500 ml) was added
  10. customthe phases separated
  11. washThe ethyl acetate solution of (S)-2-ethoxy-3-[4-(2-{4-methanesulfonyloxyphenyl}ethoxy)phenyl]propanoic acid was then washed with water (700 ml)
  12. customafter separation
  13. customevaporated to dryness
  14. customThe remaining oil was then used in the following crystallisation

Sources & evidence

ORD record
ord-5bfa979c09674ae1822570ca344c398f
Source dataset
uspto-grants-2003_03
Patent number
US06531622B1

Reaction notes

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