Methanol → 2'-Chloro-2-(methoxymethyl)biphenyl-4-carboxylic acid

HRID 2410497Notes

Reaction equation

HRID 2410497 reaction equation
[Cl: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>[Cl: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 58554216Methyl 2'-chloro-2-(methoxymethyl)biphenyl-4-carboxylate

Product 1

HCID 580662912'-Chloro-2-(methoxymethyl)biphenyl-4-carboxylic acidYield 72%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of methyl 2′-chloro-2-(methoxymethyl)biphenyl-4-carboxylate (11 g, 37.8 mmol) in a mixture of THF (50 ml), MeOH (50 ml) and water (25 ml) was added lithium hydroxide monohydrate (4.76 g, 113.5 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 (2×100 mL). 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 (7.5 g, 72%). LC/MS (Method B): 275.0 (M−H)−. 1H NMR (DMSO-d6, 400 MHz) δ 13.0 (1H, brs), 8.08 (1H, s), 7.92 (1H, d), 7.58 (1H, d), 7.44 (2H, m), 7.29 (2H, m), 4.21 (1H, d), 4.13 (1H, d), 3.16 (3H, s).

Workup

  1. concentrationthe reaction mixture was concentrated
  2. extractionextracted with EtOAc (2×100 mL)
  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-561f6e93fc2e4b249abc58ef5b38f2ac
Source dataset
uspto-grants-2014_08
Patent number
US08815919B2

Reaction notes

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