Ammonium Chloride → 3-(4-Bromo-phenyl)-N-methoxy-N-methyl-3-o-tolyl-propionamide

HRID 1617504Notes

Reaction equation

HRID 1617504 reaction equation
[Br:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=2[CH3:19])[CH2:9][C:10](O)=[O:11])=[CH:4][CH:3]=1.CN([C:23]([O:27][N:28]1N=NC2C=CC=C[C:29]1=2)=[N+](C)C)C.[B-](F)(F)(F)F.Cl.CNOC.[NH4+].[Cl-]>CN(C=O)C.CCN(CC)CC>[Br:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=2[CH3:19])[CH2:9][C:10]([N:28]([O:27][CH3:23])[CH3:29])=[O:11])=[CH:4][CH:3]=1

Participants

7

Reactant 4

HCID 25517Ammonium ChlorideHCID 81138Methanamine, N-methoxy-, hydrochloride (1:1)HCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 670156223-(4-Bromophenyl)-3-o-tolylpropanoic acid

Product 1

HCID 866609493-(4-Bromo-phenyl)-N-methoxy-N-methyl-3-o-tolyl-propionamideYield 97.6%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8471TriethylamineSolvent

Procedure

To a solution of 3-(4-bromo-phenyl)-3-o-tolyl-propionic acid (3.7 g) in DMF (45 mL) was added TBTU (5.2 g) and Et3N (4.8 mL) at 0° C. The reaction mixture was stirred at rt for 10 min and again cooled down to 0° C. N,O-dimethylhydroxylamine hydrochloride (1.36 g) was added and the mixture was stirred at rt for 1.5 hour. A saturated solution of NH4Cl was added, the phases were separated and the inorganic one was extracted with EtOAc (2×). The combined organic layers were washed with brine, dried over Na2SO4, filtered and concentrated in vacuo. The crude product was purified by flash chromatography on silica gel (EtOAc/n-heptane 1:2) to yield the title compound as a colorless oil (4.1 g, 97%), MS (ESI+): m/z=362.0750 ([M+H]+, 1Br).

Workup

  1. temperatureagain cooled down to 0° C
  2. stirringthe mixture was stirred at rt for 1.5 hour
  3. customthe phases were separated
  4. extractionthe inorganic one was extracted with EtOAc (2×)
  5. washThe combined organic layers were washed with brine
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customThe crude product was purified by flash chromatography on silica gel (EtOAc/n-heptane 1:2)

Sources & evidence

ORD record
ord-c1523339e0e24b3b9102744ff3397652
Source dataset
uspto-grants-2014_07
Patent number
US08765730B2

Reaction notes

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