Benzyl 2-(4-((2-(benzyloxy)ethoxy)methyl)-3-fluorophenyl)acrylate → 2-(3-Fluoro-4-((2-hydroxyethoxy)methyl)phenyl)propanoic acid

HRID 1842931Notes

Reaction equation

HRID 1842931 reaction equation
C([O:8][CH2:9][CH2:10][O:11][CH2:12][C:13]1[CH:18]=[CH:17][C:16]([C:19](=[CH2:30])[C:20]([O:22]CC2C=CC=CC=2)=[O:21])=[CH:15][C:14]=1[F:31])C1C=CC=CC=1>CCOC(C)=O.[OH-].[OH-].[Pd+2]>[F:31][C:14]1[CH:15]=[C:16]([CH:19]([CH3:30])[C:20]([OH:22])=[O:21])[CH:17]=[CH:18][C:13]=1[CH2:12][O:11][CH2:10][CH2:9][OH:8]

Participants

4

Reactant 1

HCID 86672151Benzyl 2-(4-((2-(benzyloxy)ethoxy)methyl)-3-fluorophenyl)acrylate

Product 1

HCID 708158662-(3-Fluoro-4-((2-hydroxyethoxy)methyl)phenyl)propanoic acidYield 36%

Reagents, catalysts & solvents 2

HCID 9942167Palladium hydroxideCatalystHCID 8857Ethyl AcetateSolvent

Procedure

A suspension of benzyl 2-(4-((2-(benzyloxy)ethoxy)methyl)-3-fluorophenyl)acrylate (2.2 g, 5.23 mmol), 10% Pd(OH)2 (300 mg) in EtOAc (20 mL) was hydrogenated (balloon pressure) at RT for 2 h until complete consumption of benzyl 2-(4-((2-(benzyloxy)ethoxy)methyl)-3-fluorophenyl)acrylate, as evidenced by TLC analysis. The reaction mixture was filtered through Celite, washed with MeOH (2×15 mL). The combined filtrate was concentrated and the obtained crude compound was purified by dissolving in EtOAc (30 mL) and shaken with aq 10% NaHCO3 solution (12 mL). The EtOAc layer was separated; the aq layer was acidified with aq. citric acid solution (pH˜5) and extracted with EtOAc (2×30 mL). The combined EtOAc layer was washed with water (10 mL), brine (10 mL) dried over anhydrous NaSO4, filtered and concentrated to afford 2-(3-fluoro-4-((2-hydroxyethoxy)methyl)phenyl)propanoic acid (450 mg, 36%) as colorless oil (TLC solvent system: 100% EtOAc; Rf: 0.15).

Workup

  1. customat RT
  2. customfor 2 h
  3. customuntil complete consumption of benzyl 2-(4-((2-(benzyloxy)ethoxy)methyl)-3-fluorophenyl)acrylate
  4. filtrationThe reaction mixture was filtered through Celite
  5. washwashed with MeOH (2×15 mL)
  6. concentrationThe combined filtrate was concentrated
  7. customthe obtained crude compound
  8. customwas purified
  9. dissolutionby dissolving in EtOAc (30 mL)
  10. customThe EtOAc layer was separated
  11. extractionextracted with EtOAc (2×30 mL)
  12. washThe combined EtOAc layer was washed with water (10 mL), brine (10 mL)
  13. dry with materialdried over anhydrous NaSO4
  14. filtrationfiltered
  15. concentrationconcentrated

Sources & evidence

ORD record
ord-6f9cf909d9e14fef8dc0395654e8c65f
Source dataset
uspto-grants-2015_02
Patent number
US08946204B2

Reaction notes

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