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

HRID 457971

Reaktionsgleichung

Reaktionsgleichung von HRID 457971
[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

Komponenten

6

Edukt 4

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

Produkt 1

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

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 176Acetic AcidLösungsmittel

Reaktionsbedingungen

Temperatur
120 °C

Versuchsvorschrift

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 refllux 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, 1 H), 7.30–7.29 (m, 2 H), 7.26 (s, 1 H), 7.14 (d, J=8.1 Hz, 1 H), 6.64 (d, J=10.8, 1 H), 6.48 (bd s, 1 H), 4.62 (d, J=5.7 Hz, 2 H), 2.19 (8, 3 H); 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.

Aufarbeitung

  1. customwas equipped with a refllux 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)

Quellen und Nachweise

ORD-Eintrag
ord-9f919c768ebb48e8a8a7a5bf8d361bb6
Quelldatensatz
uspto-grants-2007_03
Patentnummer
US07189749B2

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