Tetrahydrofuran → Aleglitazar

HRID 479124Notes

Reaction equation

HRID 479124 reaction equation
C([C@H]1COC(=O)N1C(=O)[C@@H:15]([O:41][CH3:42])[CH2:16][C:17]1[C:22]2[S:23][CH:24]=[CH:25][C:21]=2[C:20]([O:26][CH2:27][CH2:28][C:29]2[N:30]=[C:31]([C:35]3[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=3)[O:32][C:33]=2[CH3:34])=[CH:19][CH:18]=1)C1C=CC=CC=1.[OH-:44].[Na+].C1[CH2:50][O:49]CC1>>[CH3:42][O:41][C@@H:15]([CH2:16][C:17]1[C:22]2[S:23][CH:24]=[CH:25][C:21]=2[C:20]([O:26][CH2:27][CH2:28][C:29]2[N:30]=[C:31]([C:35]3[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=3)[O:32][C:33]=2[CH3:34])=[CH:19][CH:18]=1)[C:50]([OH:49])=[O:44]

Participants

4

Reactant 3

HCID 8028TetrahydrofuranHCID 14798Sodium HydroxideHCID 11444748(S)-4-Benzyl-3-((2S)-2-methoxy-3-{4-[2-(5-methyl-2-phenyl-oxazol-4-yl)-ethoxy]-benzo[b]thiophen-7-yl}-propionyl)-oxazolidin-2-one

Product 1

HCID 10274777Aleglitazar

Procedure

0.195 g of the above prepared (S)-4-benzyl-3-((2S)-2-methoxy-3-{4-[2-(5-methyl-2-phenyl-oxazol-4-yl)-ethoxy]-benzo[b]thiophen-7-yl}-propionyl)-oxazolidin-2-one (0.32 mmol) was dissolved in 2.25 ml of THF and treated with 0.81 ml of 1N NaOH (2.5 eq.). The reaction mixture was kept at 0° and progress of the hydrolysis followed by TLC. After 1 h the reaction mixture was quenched by pouring onto crashed ice/HCl. Twofold extraction with AcOEt, washing with water and brine, drying over magnesium sulfate, and evaporation of the solvents left a crude product, which was purified by twofold crystallisation from AcOEt/hexane to remove the chiral auxiliary. Thereby, 0.102 g of the title compound was obtained as white solid, mp.118-120°. The enantiomeric excess was judged according to 1H-NMR in the presence of a large excess of optically pure trifluoromethyl-anthryl-ethanol to be >95%. According to chiral HPLC (Chiralpak-AD) it amounts to 99.3%.

Workup

  1. customwas kept at 0°
  2. customAfter 1 h the reaction mixture was quenched
  3. additionby pouring
  4. extractionTwofold extraction with AcOEt
  5. washwashing with water and brine
  6. dry with materialdrying over magnesium sulfate, and evaporation of the solvents
  7. waitleft a crude product, which
  8. customwas purified by twofold crystallisation from AcOEt/hexane
  9. customto remove the chiral auxiliary

Sources & evidence

ORD record
ord-2ed97b20915840d9acde9731811a5f31
Source dataset
uspto-grants-2003_11
Patent number
US06642389B2

Reaction notes

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