Oxygen → Aleglitazar

HRID 2098339Notes

Reaction equation

HRID 2098339 reaction equation
O=O.[CH3:3][O:4]/[C:5](=[CH:9]\[C:10]1[C:15]2[S:16][CH:17]=[CH:18][C:14]=2[C:13]([O:19][CH2:20][CH2:21][C:22]2[N:23]=[C:24]([C:28]3[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=3)[O:25][C:26]=2[CH3:27])=[CH:12][CH:11]=1)/[C:6]([OH:8])=[O:7].C1([C@@H](N)C)C=CC=CC=1.[H][H]>O1CCCC1.CO>[CH3:3][O:4][C@@H:5]([CH2:9][C:10]1[C:15]2[S:16][CH:17]=[CH:18][C:14]=2[C:13]([O:19][CH2:20][CH2:21][C:22]2[N:23]=[C:24]([C:28]3[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=3)[O:25][C:26]=2[CH3:27])=[CH:12][CH:11]=1)[C:6]([OH:8])=[O:7]

Participants

7

Reactant 4

HCID 977OxygenHCID 758181-Phenethylamine, (-)-HCID 54578728(Z)-2-Methoxy-3-{4-[2-(5-methyl-2-phenyl-oxazol-4-yl)-ethoxy]-benzo[b]thiophen-7-yl}-acrylic AcidHCID 178418361HCID 178418361, compound

Product 1

HCID 10274777Aleglitazar

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

In a glove box (O2 content≦2 ppm), a 185-ml stainless steel autoclave was charged with 2.00 g of (Z)-2-methoxy-3-{4-[2-(5-methyl-2-phenyl-oxazol-4-yl)-ethoxy]-benzo[b]thiophen-7-yl}-acrylic acid (4.59 mmol), 4.48 mg of [Ir((S,S)-DBT-Bn-SIPHOX)(COD)]BARF (0.0023 mmol, S/C 2,000), 24 ml of methanol, 16 ml of tetrahydrofuran and 0.12 ml of (S)-1-phenylethylamine (0.93 mmol). The autoclave was sealed and the hydrogenation was run at 60° C. for 20 h and subsequently 80° C. for 2 h under 30 bar of hydrogen. After the autoclave was opened and the yellowish solution was rotary evaporated to dryness (50° C./5 mbar) to afford crude (S)-2-methoxy-3-{4-[2-(5-methyl-2-phenyl-oxazol-4-yl)-ethoxy]-benzo[b]thiophen-7-yl}-propionic acid (Acid I) as a white solid with a chemical purity of 99.2% (>99.9% conversion) and an enantiomeric purity of 99.4%.

Workup

  1. customThe autoclave was sealed
  2. customthe yellowish solution was rotary evaporated to dryness (50° C./5 mbar)

Sources & evidence

ORD record
ord-db4d070410d645d1a15bf130440d2ad0
Source dataset
uspto-grants-2013_05
Patent number
US08450496B2

Reaction notes

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