Oxygen → (S)-2-(4-Fluorophenyl)-3-methylbutyric acid

HRID 1416086Notes

Reaction equation

HRID 1416086 reaction equation
O=O.[F:3][C:4]1[CH:9]=[CH:8][C:7]([C:10](=[C:14]([CH3:16])[CH3:15])[C:11]([OH:13])=[O:12])=[CH:6][CH:5]=1>CO.[Ru]>[F:3][C:4]1[CH:5]=[CH:6][C:7]([C@H:10]([CH:14]([CH3:16])[CH3:15])[C:11]([OH:13])=[O:12])=[CH:8][CH:9]=1

Participants

5

Reactant 2

HCID 977OxygenHCID 110197243-Methyl-2-(p-fluorophenyl)crotonic acid

Product 1

HCID 11112309(S)-2-(4-Fluorophenyl)-3-methylbutyric acidYield 97.5%

Reagents, catalysts & solvents 2

HCID 23950RutheniumCatalystHCID 887MethanolSolvent2×

Procedure

Ruthenium-catalyzed hydrogenation. -- A catalyst solution was prepared in a glove box (O2 content <1 ppm) by dissolving 0.418 g (0.544 mmol) of Ru(OAc)2 [(R)-BlPHEMP] in 100 ml of methanol and stirring at RT for 10 minutes. Then, 211.2 g (1.0875 mol) of 2-(p-fluorophenyl)-3-methylcrotonic acid and 700 ml of methanol were placed in a 2 l autoclave and the catalyst solution prepared above was added. The autoclave was sealed and the hydrogenation was carried out while stirring at 10° and under a pressure of 150-180 bar. The conversion was 100% after 24 hours. The hydrogenation solution was evaporated at 50°/200 mbar and the residue was distilled at 108-110°/ 0.01 mbar. There were obtained 208.1 g (97.5%) of (S)-2-(p-fluorophenyl)-3-methylbutyric acid as a colorless oil which solidified at RT; m.p. 53-56°; 96.6% ee.

Workup

  1. customthe catalyst solution prepared
  2. additionabove was added
  3. customThe autoclave was sealed
  4. stirringwhile stirring at 10° and under a pressure of 150-180 bar
  5. customafter 24 hours
  6. customThe hydrogenation solution was evaporated at 50°/200 mbar
  7. distillationthe residue was distilled at 108-110°/ 0.01 mbar

Sources & evidence

ORD record
ord-25229741784c49c492f2924a31261f48
Source dataset
uspto-grants-1999_06
Patent number
US05910606

Reaction notes

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