4-Bromoanisole → HCID 67015565, compound

HRID 1617611Notes

Reaction equation

HRID 1617611 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([O:8][CH3:9])=[CH:4][CH:3]=1.C([Li])CCC.[Br:15][C:16]1[CH:21]=[CH:20][C:19]([CH:22]([C:30]2[CH:35]=[CH:34][CH:33]=[CH:32][C:31]=2[CH3:36])[CH2:23][C:24](N(OC)C)=[O:25])=[CH:18][CH:17]=1.[Cl-].[NH4+]>C1COCC1.O>[Br:15][C:16]1[CH:17]=[CH:18][C:19]([CH:22]([C:30]2[CH:35]=[CH:34][CH:33]=[CH:32][C:31]=2[CH3:36])[CH2:23][C:24]([C:2]2[CH:7]=[CH:6][C:5]([O:8][CH3:9])=[CH:4][CH:3]=2)=[O:25])=[CH:20][CH:21]=1

Participants

7

Reactant 4

HCID 77304-BromoanisoleHCID 25517Ammonium ChlorideHCID 866609493-(4-Bromo-phenyl)-N-methoxy-N-methyl-3-o-tolyl-propionamideHCID 178418339Butyllithium

Product 1

HCID 67015565HCID 67015565, compoundYield 86.3%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

A stirred solution of 4-bromoanisole (639 mg) in THF (15 ml) under argon was cooled to −78° C. A solution of n-butyllithium (2.07 ml, 1.6 M in hexane) was added slowly while keeping the temperature below −70° C. After stirring for 40 min, a solution of 3-(4-bromo-phenyl)-N-methoxy-N-methyl-3-o-tolyl-propionamide (400 mg, example 74, step 4) in THF (15 ml) was added while keeping the temperature below −70° C. The mixture was stirred at this temperature for 1 hour. The reaction was stopped by addition of saturated aqueous ammonium chloride solution (15 ml). Water was added and the mixture was extracted with ethyl acetate (3×). The combined organic phase was washed with water and brine, dried using MgSO4, filtered and concentrated to dryness. The product was purified by chromatography (SiO2, cyclohexane/ethyl acetate 1:0 to 3:2) to give the title compound (390 mg) as a light yellow oil, MS (ESI+): m/z=409.2 [M+H]+.

Workup

  1. customthe temperature below −70° C
  2. customthe temperature below −70° C
  3. stirringThe mixture was stirred at this temperature for 1 hour
  4. extractionthe mixture was extracted with ethyl acetate (3×)
  5. washThe combined organic phase was washed with water and brine
  6. customdried
  7. filtrationfiltered
  8. concentrationconcentrated to dryness
  9. customThe product was purified by chromatography (SiO2, cyclohexane/ethyl acetate 1:0 to 3:2)

Sources & evidence

ORD record
ord-c895aba6be6445f2980f30615c8e7709
Source dataset
uspto-grants-2014_07
Patent number
US08765730B2

Reaction notes

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