Hydrochloric Acid → (2-(((4-Bromo-2-fluorobenzyl)amino)carbonyl)-5-chlorophenoxy)acetic acid

HRID 457941Notes

Reaction equation

HRID 457941 reaction equation
C([O:3][C:4](=[O:26])[CH2:5][O:6][C:7]1[CH:12]=[C:11]([Cl:13])[CH:10]=[CH:9][C:8]=1[C:14](=[O:25])[NH:15][CH2:16][C:17]1[CH:22]=[CH:21][C:20]([Br:23])=[CH:19][C:18]=1[F:24])C.[OH-].[Na+].Cl>C(O)C.C(OCC)(=O)C>[Br:23][C:20]1[CH:21]=[CH:22][C:17]([CH2:16][NH:15][C:14]([C:8]2[CH:9]=[CH:10][C:11]([Cl:13])=[CH:12][C:7]=2[O:6][CH2:5][C:4]([OH:26])=[O:3])=[O:25])=[C:18]([F:24])[CH:19]=1

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 22093478[2-(4-Bromo-2-fluoro-benzylcarbamoyl)-5-chloro-phenoxy]-acetic acid ethyl ester

Product 1

HCID 16058629(2-(((4-Bromo-2-fluorobenzyl)amino)carbonyl)-5-chlorophenoxy)acetic acidYield 97%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 8857Ethyl AcetateSolvent

Procedure

A solution of [2-(4-bromo-2-fluoro-benzylcarbamoyl)-5-chloro-phenoxy]-acetic acid ethyl ester (3.20 g, 7.20 mmol) in ethanol (36 mL, 0.2 M) was cooled to 0° C. and treated with aq NaOH (1.25 M, 28.8 mL, 36.0 mmol). After stirring for 30 min, the solution was warmed to room temperature and stirred an additional 4 h. Next, the solution was acidified to pH 1–2 with 2 N HCl, diluted with ethyl acetate and washed with saturated aq NaCl. The organic layer was dried over Na2SO4, filtered and concentrated to give [2-(4-bromo-2-fluoro-benzylcarbamoyl)-5-chloro-phenoxy]-acetic acid as a white crystalline solid (2.91 g, 97%): mp 184–185° C.; Rf 0.31 (20% methanol in dichloromethane); 1H NMR (DMSO-d6, 300 MHz) δ 13.40 (br s, 1 H), 9.05, (t, J=5.7 Hz. 1 H), 7.83, (d, J=8.4 Hz, 1 H), 7.48 (d, J=10.5 Hz, 1 Hz), 7.38–7.32 (m, 2 H), 7.26 (d, J=1.8 Hz, 1 H), 7.13 (dd, J=8.4 Hz, J2=1.5 Hz, 1 H), 4.91 (s, 2 H), 4.49 (d, J=5.7 Hz, 2 H). ESI-LC/MS m/z calcd for C16H12BrClFNO4: 416.6; found 418.0 (M+1)+. Anal. calcd for C16H12BrClFNO4: C, 46.13; H, 2.90; N, 3.36; Cl, 17.02. Found C, 46.04; H, 2.89; N, 3.31; Cl, 17.09.

Workup

  1. stirringstirred an additional 4 h
  2. washwashed with saturated aq NaCl
  3. dry with materialThe organic layer was dried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated

Sources & evidence

ORD record
ord-2b96b4f9f5354677a742ca2f747178d1
Source dataset
uspto-grants-2007_03
Patent number
US07189749B2

Reaction notes

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