Hydrochloric Acid → N-(4-bromo-2-fluoro-benzyl)-2-hydroxy-4-methoxy-benzamide

HRID 457943

Reaction equation

HRID 457943 reaction equation
[Br:1][C:2]1[CH:22]=[CH:21][C:5]([CH2:6][N:7]2[C:12](=[O:13])[C:11]3[CH:14]=[CH:15][C:16]([O:18][CH3:19])=[CH:17][C:10]=3[O:9]C2=O)=[C:4]([F:23])[CH:3]=1.[OH-].[K+].Cl>C(O)C>[Br:1][C:2]1[CH:22]=[CH:21][C:5]([CH2:6][NH:7][C:12](=[O:13])[C:11]2[CH:14]=[CH:15][C:16]([O:18][CH3:19])=[CH:17][C:10]=2[OH:9])=[C:4]([F:23])[CH:3]=1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 14797Potassium HydroxideHCID 184681743-(4-Bromo-2-fluoro-benzyl)-7-methoxy benzo[e][1,3]oxazine-2,4-dione

Product 1

HCID 18468133N-(4-bromo-2-fluoro-benzyl)-2-hydroxy-4-methoxy-benzamideYield 71%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

A solution of 3-(4-bromo-2-fluoro-benzyl)-7-methoxy benzo[e] [1,3] oxazine-2,4-dione (1.67 g, 4.4 mmol) in ethanol (80 mL, 0.06 M) was cooled to 0° C. and treated with aq KOH (0.673 g, 11.9 mmol, 1.2 M). After 3 h, the reaction was acidified to pH 1–2 with 2 N HCl and extracted with ethyl acetate (3×). The combined organic extracts were washed with saturated aq NaCl, dried over Na2SO4, filtered and concentrated. The crude solid was recrystallized from heptane and ethyl acetate to give N-(4-bromo-2-fluoro-benzyl)-2-hydroxy-4-methoxy-benzamide as a white crystalline solid (1.10 g, 71%): mp 128–129.5° C.; Rf 0.28 (25% ethyl acetate in heptane); 1H NMR (DMSO-d6, 300 MHz) δ 12.70 (br s, 1 H), 9.14 (br t, J=5.2 Hz, 1 H), 7.80 (d, J=8.5 Hz, 1 H), 7.50 (d, J=8.5 Hz, 1 H), 7.40–7.25 (m, 2 H), 6.50–6.48 (m, 2 H), 4.45 (d, J=5.2 Hz, 2 H), 3.75 (s, 3 H). ESI-LC/MS m/z calcd for C15H13BrFNO2: 353.0; found 352.0 (M−1)−. Anal. calcd for C15H13BrFNO2: C, 50.87; H, 3.70; N, 3.95. Found C, 50.70; H, 3.73; N, 3.91.

Workup

  1. extractionextracted with ethyl acetate (3×)
  2. washThe combined organic extracts were washed with saturated aq NaCl
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe crude solid was recrystallized from heptane and ethyl acetate

Sources & evidence

ORD record
ord-9b01dda2d9ee4925828ed3a24f096f09
Source dataset
uspto-grants-2007_03
Patent number
US07189749B2

Linked notes

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