Sodium Hydroxide → [2-(4-Bromo-2-fluoro-benzylcarbamoyl)-5-fluoro-4-methyl-phenoxy]-acetic acid

HRID 457973Notes

Reaction equation

HRID 457973 reaction equation
C([O:3][C:4](=[O:27])[CH2:5][O:6][C:7]1[CH:12]=[C:11]([F:13])[C:10]([CH3:14])=[CH:9][C:8]=1[C:15](=[O:26])[NH:16][CH2:17][C:18]1[CH:23]=[CH:22][C:21]([Br:24])=[CH:20][C:19]=1[F:25])C.[OH-].[Na+]>C(O)C>[Br:24][C:21]1[CH:22]=[CH:23][C:18]([CH2:17][NH:16][C:15]([C:8]2[CH:9]=[C:10]([CH3:14])[C:11]([F:13])=[CH:12][C:7]=2[O:6][CH2:5][C:4]([OH:27])=[O:3])=[O:26])=[C:19]([F:25])[CH:20]=1

Participants

4

Reactant 2

HCID 14798Sodium HydroxideHCID 22093479(2-(4-Bromo-2-fluoro-benzylcarbamoyl)-5-fluoro-4-methyl-phenoxy]-acetic acid ethyl ester

Product 1

HCID 22093452[2-(4-Bromo-2-fluoro-benzylcarbamoyl)-5-fluoro-4-methyl-phenoxy]-acetic acidYield 98.4%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

A stirring solution of [2-(4-bromo-2-fluoro-benzylcarbamoyl)-5-fluoro-4-methyl-phenoxy]-acetic acid ethyl ester (0.72 g, 1.62 mmol) in ethanol (8.1 mL, 0.2 M) was placed in an ice bath and treated with aq NaOH (1.25 M, 7.8 mL, 9.73 mmol). The mixture was gradually allowed to warm to room temperature and after two hours the mixture was concentrated under reduced pressure, diluted with ethyl acetate, and treated with 2 N HCl (10 mL). The separated organic layer was washed with saturated aq NaCl. The organic layer was dried over Na2SO4, filtered, and concentrated to afford [2-(4-bromo-2-fluoro-benzylcarbamoyl)-5-fluoro-4-methyl-phenoxy]-acetic acid (0.66 g, 98%) as a white solid: mp 169° C.; Rf 0.22 (20% methanol in dichloromethane); 1H NMR (DMSO-d6, 0.300 MHz) δ 9.00 (bd t, J=5.3 Hz, 1 H), 7.76 (d, J=9.6 Hz, 1 H), 7.49 (d, J=9.6 Hz, 1 H), 7.39–7.33 (m, 2 H), 7.04 (dd, J1=11.4 Hz, J2=1.4 Hz, 1 H), 4.84 (d, J=1.8 Hz, 2 H), 4.48 (bd 8, 2 H), 2.17 (s, 3 H); ESI-LC/MS m/z calcd for C17H14BrF2NO4: 413.0; found 412 (M−1)−. Anal. calcd for C17H14BrF2NO4: C, 49.30; H, 3.41; N, 3.38. Found C, 49.32; H, 3.43; Br, 3.32.

Workup

  1. concentrationwas concentrated under reduced pressure
  2. additiondiluted with ethyl acetate
  3. additiontreated with 2 N HCl (10 mL)
  4. washThe separated organic layer was washed with saturated aq NaCl
  5. dry with materialThe organic layer was dried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-da000b9fc32b4568ac6cd140c09943fa
Source dataset
uspto-grants-2007_03
Patent number
US07189749B2

Reaction notes

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