HCID 20559791, compound → Flurbiprofen Methyl Ester

HRID 1449052Notes

Reaction equation

HRID 1449052 reaction equation
[F:1][C:2]1[CH:7]=[C:6]([C:8](O)([CH3:13])[C:9]([O:11][CH3:12])=[O:10])[CH:5]=[CH:4][C:3]=1[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1>S(Cl)(Cl)=O>[F:1][C:2]1[CH:7]=[C:6]([CH:8]([CH3:13])[C:9]([O:11][CH3:12])=[O:10])[CH:5]=[CH:4][C:3]=1[C:15]1[CH:16]=[CH:17][CH:18]=[CH:19][CH:20]=1

Participants

3

Reactant 1

HCID 20559791HCID 20559791, compound

Product 1

HCID 4127Flurbiprofen Methyl Ester

Reagents, catalysts & solvents 1

HCID 24386Thionyl ChlorideSolvent

Conditions

Temperature
50 °C

Procedure

The product of Example I (5 g.) was heated under reflux with methanol (50 ml.) and concentrated sulphuric acid (1 ml.) for 4 hours. The product was poured into water, extracted with ether, the ether extracts dried and evaporated to give methyl 2-(2-fluoro-4-biphenylyl)-2-hydroxypropionate, m.p. 59°-61° C. This ester (1 g.) was dissolved in thionyl chloride (5 ml.) and heated on a water bath at 50° C. for two hours. Thionyl chloride was removed and the product was applied to preparative thin layer chromatography plates, eluted with an ether/petroleum (b.p. 62°-68° C.) mixture (5%:95%) and methyl 2-chloro-2-(2-fluoro-4-biphenylyl)propionate recovered. This was dissolved in ethyl acetate (5 ml.) and hydrogenated at room temperature using a 10% palladium/charcoal catalyst (73 mg.) for 16 hours. The solution was filtered and evaporated to give methyl 2-(2-fluoro-4-biphenylyl)propionate, whose structure was confirmed by n.m.r. This was hydrolysed by heating under reflux with aqueous ethanolic potassium hydroxide. The solution was acidified, extracted with ether and then aqueous potassium carbonate (10%) and this extract acidified and the precipitate collected to give 2-(2-fluoro-4-biphenylyl)propionic acid (m.p.t. 105°-106° C.).

Workup

  1. customThionyl chloride was removed
  2. washeluted with an ether/petroleum (b.p. 62°-68° C.) mixture (5%:95%) and methyl 2-chloro-2-(2-fluoro-4-biphenylyl)propionate
  3. customrecovered
  4. dissolutionThis was dissolved in ethyl acetate (5 ml.) and hydrogenated at room temperature
  5. customfor 16 hours
  6. filtrationThe solution was filtered
  7. customevaporated

Sources & evidence

ORD record
ord-661f2faa54c7454cbc3f6028fdd0eba1
Source dataset
uspto-grants-1980_02
Patent number
US04188491

Reaction notes

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