Methanol → 2'-Fluoro-2-(methoxymethyl)-[1,1'-biphenyl]-4-carboxylic acid

HRID 1630990Notes

Reaction equation

HRID 1630990 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[CH:13]=[CH:12][C:11]([C:14]([O:16]C)=[O:15])=[CH:10][C:9]=1[CH2:18][O:19][CH3:20].CO.O.O.[OH-].[Li+]>C1COCC1>[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[CH:13]=[CH:12][C:11]([C:14]([OH:16])=[O:15])=[CH:10][C:9]=1[CH2:18][O:19][CH3:20]

Participants

6

Reactant 4

HCID 887MethanolHCID 962WaterHCID 168937Lithium hydroxide, monohydrateHCID 58554102Methyl 2'-fluoro-2-(methoxymethyl)-[1,1'-biphenyl]-4-carboxylate

Product 1

HCID 580663712'-Fluoro-2-(methoxymethyl)-[1,1'-biphenyl]-4-carboxylic acidYield 92.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of methyl 2′-fluoro-2-(methoxymethyl)biphenyl-4-carboxylate (12 g, 43.7 mmol) in a mixture of THF (50 ml), MeOH (50 ml) and water (25 ml) was added lithium hydroxide monohydrate (5.50 g, 131.2 mmol) in portions. After 12 hours at RT, the reaction mixture was concentrated and the aqueous residual layer was acidified with a concentrated aqueous solution of HCl, and then extracted with EtOAc. The organic layers were washed with water and brine, combined, dried (Na2SO4) and concentrated under reduced pressure to afford of the title compound as a white solid (10.5 g, 92%). LC/MS, M−(ESI): 259.0. 1H NMR (DMSO-d6, 400 MHz) δ 13.07 (1H, brs), 8.10 (1H, s), 7.92 (1H, d), 7.48 (1H, m), 7.27-7.37 (4H, m), 4.26 (2H, s), 3.18 (3H, s).

Workup

  1. concentrationthe reaction mixture was concentrated
  2. extractionextracted with EtOAc
  3. washThe organic layers were washed with water and brine
  4. dry with materialdried (Na2SO4)
  5. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-70e2e38a73eb4b94a9a2a712a883cc65
Source dataset
uspto-grants-2014_07
Patent number
US08791142B2

Reaction notes

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