Sodium Hydroxide → 4-(3,5-Difluorophenyl)butanoic acid

HRID 2201626Notes

Reaction equation

HRID 2201626 reaction equation
C([O:4][C:5](=[O:17])[CH2:6][CH2:7][CH2:8][C:9]1[CH:14]=[C:13]([F:15])[CH:12]=[C:11]([F:16])[CH:10]=1)CC.[OH-].[Na+]>O>[F:15][C:13]1[CH:14]=[C:9]([CH2:8][CH2:7][CH2:6][C:5]([OH:17])=[O:4])[CH:10]=[C:11]([F:16])[CH:12]=1

Participants

4

Reactant 2

HCID 14798Sodium HydroxideHCID 667554994-(3,5-Difluoro-phenyl)-butyric acid propyl ester

Product 1

HCID 196994854-(3,5-Difluorophenyl)butanoic acidYield 102.7%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
50 °C

Procedure

A mixture of crude 4-(3,5-difluoro-phenyl)-butyric acid propyl ester (3.3 kg), water (4.4 kg), and 50% sodium hydroxide (3.35 kg) were stirred at 50° C. for 1 hour. The hydrolysis was monitored by HPLC. The resulting solution was washed with hexane (4.2 kg) to remove organic impurities. The aqueous layer was acidified with conc. HCl (4.73 kg), and extracted with MTBE (4.23 kg). The solution was concentrated, and residual MTBE was removed by solvent exchange with n-heptane (4.0 liters) to give crude 4-(3,5-difluoro-phenyl)-butyric acid (2.8 kg) as an oil: H1 NMR (300 MHz): δ(CDCl3): 1.94 (2H, p, J=7.54 Hz), 2.38 (2H, t, J=7.54 Hz), 2.65 (2H, t, J=7.54 Hz), 6.63 (1H, tt, J=2.26, 9.04 Hz), 6.7 (2H, m, J=2.26, 6.4 Hz), 11.70 (1H, bs, COOH)

Workup

  1. washThe resulting solution was washed with hexane (4.2 kg)
  2. customto remove organic impurities
  3. extractionextracted with MTBE (4.23 kg)
  4. concentrationThe solution was concentrated
  5. customresidual MTBE was removed by solvent exchange with n-heptane (4.0 liters)

Sources & evidence

ORD record
ord-2cf8ea034c534414860e06a829bb53d7
Source dataset
uspto-grants-2016_06
Patent number
US09365494B2

Reaction notes

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