Ammonium Chloride → (3-Bromo-5-ethoxy-phenyl)-(4-methoxy-3-methyl-phenyl)-methanone

HRID 1668745Notes

Reaction equation

HRID 1668745 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([O:8][CH3:9])=[C:4]([CH3:10])[CH:3]=1.[Mg].[Br:12][C:13]1[CH:14]=[C:15]([CH:22]=[C:23]([O:25][CH2:26][CH3:27])[CH:24]=1)[C:16](N(OC)C)=[O:17].[Cl-].[NH4+]>O1CCCC1>[Br:12][C:13]1[CH:14]=[C:15]([C:16]([C:2]2[CH:7]=[CH:6][C:5]([O:8][CH3:9])=[C:4]([CH3:10])[CH:3]=2)=[O:17])[CH:22]=[C:23]([O:25][CH2:26][CH3:27])[CH:24]=1

Participants

6

Reactant 4

HCID 25517Ammonium ChlorideHCID 6083154-Bromo-1-methoxy-2-methylbenzeneHCID 5462224MagnesiumHCID 578251923-bromo-5-ethoxy-N-methoxy-N-methylbenzamide

Product 1

HCID 57825029(3-Bromo-5-ethoxy-phenyl)-(4-methoxy-3-methyl-phenyl)-methanone

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent4×

Conditions

Temperature
15 °C

Procedure

A solution of 4-bromo-2-methylanisole (0.984 g, 4.9 mmol) in tetrahydrofuran (3 mL) was added dropwise to magnesium powder (0.127 g, 5.2 mmol) in tetrahydrofuran (1 mL) at room temperature. Under external heating the reaction mixture was brought up to reflux. After complete addition, reflux was maintained for 1 hour. Thereafter the mixture was cooled to 15° C., then diluted with tetrahydrofuran (1 mL) before a solution of 3-bromo-5-ethoxy-N-methoxy-N-methyl-benzamide (1.238 g, 4.3 mmol) in tetrahydrofuran (3 mL) was added dropwise. After complete addition, the mixture was heated to reflux for 1.5 hours. For the working-up, it was cooled to 5° C. and hydrolysed with a saturated solution of ammonium chloride (25 mL). The aqueous layer was extracted twice with ethyl acetate (2×50 mL), thereupon, the organic layers combined, washed with brine, dried over sodium sulfate and evaporated under reduced pressure. The crude product was chromatographed on silica gel using a gradient of heptane/ethyl acetate=100/0 to 6/1 as the eluent. There were obtained 1.16 g (77% of theory) of the title compound as a colourless oil. Mass (calculated) C17H17BrO3 [348]; (found) [M+H]+=349, 351.

Workup

  1. temperatureUnder external heating the reaction mixture
  2. temperatureto reflux
  3. additionAfter complete addition
  4. temperaturereflux
  5. temperaturewas maintained for 1 hour
  6. additionwas added dropwise
  7. additionAfter complete addition
  8. temperaturethe mixture was heated
  9. temperatureto reflux for 1.5 hours
  10. extractionThe aqueous layer was extracted twice with ethyl acetate (2×50 mL)
  11. washwashed with brine
  12. dry with materialdried over sodium sulfate
  13. customevaporated under reduced pressure
  14. customThe crude product was chromatographed on silica gel using a gradient of heptane/ethyl acetate=100/0 to 6/1 as the eluent

Sources & evidence

ORD record
ord-1370c69d0d4c426b83d74bd31d111ff8
Source dataset
uspto-grants-2011_08
Patent number
US07989449B2

Reaction notes

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