Diphenylpropionic acid → N-Methoxy-N-methyl-3,3-diphenyl-propionamide

HRID 1617500Notes

Reaction equation

HRID 1617500 reaction equation
[C:1]1([CH:7]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)[CH2:8][C:9](O)=[O:10])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.CN([C:21]([O:25][N:26]1N=NC2C=CC=C[C:27]1=2)=[N+](C)C)C.[B-](F)(F)(F)F.Cl.CNOC.C([O-])(O)=O.[Na+]>CN(C=O)C.CCN(CC)CC>[CH3:21][O:25][N:26]([CH3:27])[C:9](=[O:10])[CH2:8][CH:7]([C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1)[C:1]1[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1

Participants

7

Reactant 4

HCID 64798Diphenylpropionic acidHCID 81138Methanamine, N-methoxy-, hydrochloride (1:1)HCID 516892Sodium BicarbonateHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate

Product 1

HCID 54293842N-Methoxy-N-methyl-3,3-diphenyl-propionamideYield 85.1%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8471TriethylamineSolvent

Procedure

To a solution of 3,3-diphenylpropionic acid (CAS RN: [606-83-7], 1.5 g) in DMF (17 mL) was added TBTU (2.98 g) and Et3N (2.1 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 (0.78 g) was added and the mixture was stirred at rt for 1 hour. A saturated aqueous solution of NaHCO3 was added, the phases were separated and the inorganic one was extracted with TBME (2×). The combined organic layers were washed with 1N aqueous KHSO4 and brine, dried over Na2SO4, filtered and concentrated in vacuo. The crude product was purified by flash chromatography on silica gel (EtOAc/n-heptane 1:1) to yield the title compound (1.52 g, 85%) as a colorless oil, MS (ESI+): m/z=270.2 ([M+H]+).

Workup

  1. temperatureagain cooled down to 0° C
  2. stirringthe mixture was stirred at rt for 1 hour
  3. customthe phases were separated
  4. extractionthe inorganic one was extracted with TBME (2×)
  5. washThe combined organic layers were washed with 1N aqueous KHSO4 and 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 1:1)

Sources & evidence

ORD record
ord-7639f36869554337bd6aa90e844541ec
Source dataset
uspto-grants-2014_07
Patent number
US08765730B2

Reaction notes

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