Oxygen → Aleglitazar

HRID 2098354Notes

Reaction equation

HRID 2098354 reaction equation
O=O.CC1SC(C)=C(P(C2C=CC=CC=2)C2C=CC=CC=2)C=1C1C(P(C2C=CC=CC=2)C2C=CC=CC=2)=C(C)SC=1C.[CH3:43][O:44]/[C:45](=[CH:49]\[C:50]1[C:55]2[S:56][CH:57]=[CH:58][C:54]=2[C:53]([O:59][CH2:60][CH2:61][C:62]2[N:63]=[C:64]([C:68]3[CH:73]=[CH:72][CH:71]=[CH:70][CH:69]=3)[O:65][C:66]=2[CH3:67])=[CH:52][CH:51]=1)/[C:46]([OH:48])=[O:47].C1([C@@H](N)C)C=CC=CC=1.[H][H]>C1COCC1.CO>[CH3:43][O:44][C@@H:45]([CH2:49][C:50]1[C:55]2[S:56][CH:57]=[CH:58][C:54]=2[C:53]([O:59][CH2:60][CH2:61][C:62]2[N:63]=[C:64]([C:68]3[CH:73]=[CH:72][CH:71]=[CH:70][CH:69]=3)[O:65][C:66]=2[CH3:67])=[CH:52][CH:51]=1)[C:46]([OH:48])=[O:47]

Participants

8

Reactant 5

HCID 977OxygenHCID 758181-Phenethylamine, (-)-HCID 9963051HCID 9963051, compoundHCID 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 887MethanolSolvent2×HCID 8028TetrahydrofuranSolvent

Procedure

In a glove box (O2 content≦2 ppm), a 50-ml stainless steel autoclave was charged with 0.62 mg of [Ru(OAc)2((S)-TMBTP)] (0.0008 mmol, S/C 3′000) (prepared according to EP 1,670,792 B1; TMBTP=2,2′,5,5′-Tetramethyl-4,4′-bis(diphenylphosphino)-3,3′-bithiophene) and 5 ml of methanol. The resulting orange solution was stirred for 2 h at r.t. Then, 1.00 g of (Z)-2-methoxy-3-{4-[2-(5-methyl-2-phenyl-oxazol-4-yl)-ethoxy]-benzo[b]thiophen-7-yl}-acrylic acid (2.30 mmol), 4 ml of methanol, 6 ml of THF and 0.06 ml of (S)-1-phenylethylamine (0.47 mmol) were added. The autoclave was sealed and the hydrogenation was run under stirring at 40° C. under 30 bar of hydrogen. After 16 h 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 99.7% (99.9% conversion) and an enantiomeric purity of 89%.

Workup

  1. customThe autoclave was sealed
  2. waitAfter 16 h the autoclave was opened
  3. customthe yellowish solution was rotary evaporated to dryness (50° C./5 mbar)

Sources & evidence

ORD record
ord-56c087b87b694f3299453485aff57f78
Source dataset
uspto-grants-2013_05
Patent number
US08450496B2

Reaction notes

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