Lithium hydroxide, monohydrate → 2-(2-Ethynyl-4-fluorophenyl)acetic acid

HRID 1711088Notes

Reaction equation

HRID 1711088 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][C:9]([O:11]C)=[O:10])=[C:4]([C:13]#[C:14][Si](C)(C)C)[CH:3]=1.C1COCC1.CO.O.[OH-].[Li+]>O>[C:13]([C:4]1[CH:3]=[C:2]([F:1])[CH:7]=[CH:6][C:5]=1[CH2:8][C:9]([OH:11])=[O:10])#[CH:14]

Participants

5

Reactant 3

HCID 168937Lithium hydroxide, monohydrateHCID 21899815MeOH tetrahydrofuranHCID 59457720Methyl 2-(4-fluoro-2-((trimethylsilyl)ethynyl)phenyl)acetate

Product 1

HCID 594577442-(2-Ethynyl-4-fluorophenyl)acetic acidYield 95%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

To a solution of ester 326 (3.30 g, 12.5 mmol) in 1:1 THF/methanol (100 mL) was added lithium hydroxide monohydrate (1.60 g, 38.1 mmol) in water (25 mL) and the mixture was stirred at r.t. for 30 min. It was then partially concentrated; the aqueous residue was washed with ether; then acidified with 3M HCl (aq), extracted with ethyl acetate. The organic extract was washed with water, dried (anhydrous MgSO4), filtered and concentrated to provide acid 327 (2.10 g, 95% yield). 1H NMR (400 MHz, DMSO-d6) δ (ppm): 7.36 (dd, J=8.6, 5.9 Hz, 1H); 7.30 (dd, J=9.2, 2.7 Hz, 1H); 7.21 (dt, J=8.6, 2.7 Hz, 1H); 4.48 (s, 1H); 3.70 (s, 2H). LCMS: (M+Na) 201.1.

Workup

  1. concentrationIt was then partially concentrated
  2. washthe aqueous residue was washed with ether
  3. extractionextracted with ethyl acetate
  4. extractionThe organic extract
  5. washwas washed with water
  6. dry with materialdried (anhydrous MgSO4)
  7. filtrationfiltered
  8. concentrationconcentrated

Sources & evidence

ORD record
ord-6dc128a8cc5441a085f844776a971a2a
Source dataset
uspto-grants-2010_09
Patent number
US07790729B2

Reaction notes

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