Sodium Hydroxide → 2'-Chloro-3'-fluoro-2-(methoxymethyl)biphenyl-4-carboxylic acid

HRID 2410548Notes

Reaction equation

HRID 2410548 reaction equation
[OH-].[Na+].[Cl:3][C:4]1[C:9]([F:10])=[CH:8][CH:7]=[CH:6][C:5]=1[C:11]1[CH:16]=[CH:15][C:14]([C:17]([O:19]C)=[O:18])=[CH:13][C:12]=1[CH2:21][O:22][CH3:23]>CCO>[Cl:3][C:4]1[C:9]([F:10])=[CH:8][CH:7]=[CH:6][C:5]=1[C:11]1[CH:16]=[CH:15][C:14]([C:17]([OH:19])=[O:18])=[CH:13][C:12]=1[CH2:21][O:22][CH3:23]

Participants

4

Reactant 2

HCID 14798Sodium HydroxideHCID 66678433Methyl 2'-chloro-3'-fluoro-2-(methoxymethyl)biphenyl-4-carboxylate

Product 1

HCID 580662682'-Chloro-3'-fluoro-2-(methoxymethyl)biphenyl-4-carboxylic acid

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

A 5N aqueous solution of NaOH (2.3 mL, 11.5 mmol) was added into a solution of methyl 2′-chloro-3′-fluoro-2-(methoxymethyl)biphenyl-4-carboxylate (2.38 g, 7.7 mmol) in EtOH (25 mL) and heated at reflux for 30 minutes. The reaction mixture was concentrated under vacuum. The residue was taken up with water (30 mL) and a 5N aqueous solution of HCl (4 mL), and then extracted with MTBE (100 mL, then 50 mL). The organic layers were washed with brine, combined, dried (MgSO4) and treated with activated charcoal. After filtration through a Celite pad, the solution was concentrated under vacuum. After purification by crystallization from a mixture of MTBE and heptane, the title compound was obtained as a white powder (2.01 g, 88%). HPLC (Method A) Rt 4.1 min (Purity: 99.5%). LC/MS (Method B): 293.0 (M−H)−. 1H NMR (DMSO-d6, 300 MHz) δ 13.13 (s, 1H), 8.10 (d, J=1.7 Hz, 1H), 7.94 (dd, J=8.0, 1.7 Hz, 1H), 7.54-7.44 (m, 2H), 7.33 (d, J=8.0 Hz, 1H), 7.23-7.18 (m, 1H), 4.23 (d, J=12.7 Hz, 1H), 4.15 (d, J=12.7 Hz, 1H), 3.17 (s, 3H).

Workup

  1. temperatureheated
  2. temperatureat reflux for 30 minutes
  3. concentrationThe reaction mixture was concentrated under vacuum
  4. extractiona 5N aqueous solution of HCl (4 mL), and then extracted with MTBE (100 mL
  5. washThe organic layers were washed with brine
  6. dry with materialdried (MgSO4)
  7. additiontreated with activated charcoal
  8. filtrationAfter filtration through a Celite pad
  9. concentrationthe solution was concentrated under vacuum
  10. customAfter purification
  11. customby crystallization
  12. additionfrom a mixture of MTBE and heptane

Sources & evidence

ORD record
ord-2fa97abbd8424b2faff89dda61921e13
Source dataset
uspto-grants-2014_08
Patent number
US08815919B2

Reaction notes

Loading…