Hydrogen Bromide → N-(4-bromo-2-fluoro-benzyl)-4-fluoro-2-hydroxy-5-methyl-benzamide

HRID 2229558

Reaction equation

HRID 2229558 reaction equation
[Br:1][C:2]1[CH:21]=[CH:20][C:5]([CH2:6][NH:7][C:8](=[O:19])[C:9]2[CH:14]=[C:13]([CH3:15])[C:12]([F:16])=[CH:11][C:10]=2[O:17]C)=[C:4]([F:22])[CH:3]=1.Br.[Na+].[Cl-].C(OCC)(=O)C>C(O)(=O)C>[Br:1][C:2]1[CH:21]=[CH:20][C:5]([CH2:6][NH:7][C:8](=[O:19])[C:9]2[CH:14]=[C:13]([CH3:15])[C:12]([F:16])=[CH:11][C:10]=2[OH:17])=[C:4]([F:22])[CH:3]=1

Participants

6

Reactant 4

HCID 260Hydrogen BromideHCID 5234Sodium ChlorideHCID 8857Ethyl AcetateHCID 18468165N-(4-bromo-2-fluoro-benzyl)4-fluoro-2-methoxy-5-methyl-benzamide

Product 1

HCID 18468169N-(4-bromo-2-fluoro-benzyl)-4-fluoro-2-hydroxy-5-methyl-benzamideYield 73%

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Conditions

Temperature
120 °C

Procedure

A stirring suspension of N-(4-bromo-2-fluoro-benzyl)4-fluoro-2-methoxy-5-methyl-benzamide (2.32 g, 6.51 mmol) in a 25% solution of HBr in acetic acid (60 mL, 0.11 M) was equipped with a reflux condenser and heated to 120° C. for 3.5 h. The mixture was allowed to cool and saturated aq NaCl (50 mL) and ethyl acetate (50 mL) were added. The layers were allowed to separate and the organic layer was collected. The aqueous layer was extracted with ethyl acetate (2×50 mL). The combined organics were dried over Na2SO4, filtered, and concentrated to provide an orange powder. Purification of the solid via silica gel flash chromatography (30% ethyl acetate in heptane) provided N-(4-bromo-2-fluoro-benzyl)-4-fluoro-2-hydroxy-5-methyl-benzamide (1.69, 73%) as a white powder: mp 149-150° C.; Rf 0.51 (30% ethyl acetate in heptane); 1H NMR (CDCl3, 300 MHz) δ 12.20 (d, J=1.5, 1H), 7.30-7.29 (m, 2H), 7.26 (s, 1H), 7.14 (d, J=8.1 Hz, 1H), 6.64 (d, J=10.8, 1H), 6.48 (bd s, 1H), 4.62 (d, J=5.7'Hz, 2H), 2.19 (s, 3H); ESI-LC/MS m/z calcd for C15H12BrF2NO2: 355.0. Found 354.0 (M−1)−. Anal. calcd for C15H12BrF2NO2: C, 50.58; H, 3.40; N, 3.93. Found C, 50.65; H, 3.47; N, 3.87.

Workup

  1. customwas equipped with a reflux condenser
  2. temperatureto cool
  3. customto separate
  4. customthe organic layer was collected
  5. extractionThe aqueous layer was extracted with ethyl acetate (2×50 mL)
  6. dry with materialThe combined organics were dried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customto provide an orange powder
  10. customPurification of the solid via silica gel flash chromatography (30% ethyl acetate in heptane)

Sources & evidence

ORD record
ord-8dd8788bafd5445daf69f2532aa0c982
Source dataset
uspto-grants-2002_07
Patent number
US06420426B1

Linked notes

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