Water → N,N-Diethylbenzamide

HRID 2258321Notes

Reaction equation

HRID 2258321 reaction equation
C(N1[C@@H](C)CN([C@H]([C:19]2[CH:31]=[CH:30][C:22]([C:23]([N:25]([CH2:28][CH3:29])[CH2:26][CH3:27])=[O:24])=[CH:21][CH:20]=2)C2C=CC=C(O)C=2)[C@H](C)C1)C=C.O.FC(F)(F)C(O)=O>CO.[Pd]>[CH2:28]([N:25]([CH2:26][CH3:27])[C:23](=[O:24])[C:22]1[CH:30]=[CH:31][CH:19]=[CH:20][CH:21]=1)[CH3:29]

Participants

6

Reactant 3

HCID 962WaterHCID 6422Trifluoroacetic acidHCID 9806277rel-4-[(R)-[(2R,5S)-2,5-Dimethyl-4-(2-propen-1-yl)-1-piperazinyl](3-hydroxyphenyl)methyl]-N,N-diethylbenzamide

Product 1

HCID 15542N,N-Diethylbenzamide

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 887MethanolSolvent

Procedure

(±)-4-((αR*)-α-((2R*,5S*)-4-Allyl-2,5-dimethyl-1-piperazinyl)-3-hydroxybenzyl) -N-N-diethylbenzamide (Example 14) (21.75 g, 0.0499 mol) was dissolved in 330 mL methanol:90 mL water. Trifluoroacetic acid (3.9 mL, 0.0499 mol) was added, followed by 14.5 g of 5% palladium on carbon. The solution was heated at reflux for three days and filtered through Celite. The solvent was removed, and the residue was purified by chromatography on silica gel with ethanol (0-20%) in dichloromethane containing 1% tdethylamine. The solvent was removed, and the residue was redissolved in dichloromethane and washed with water at pH 8. The organic layer was dried over sodium sulfate and concentrated to dryness. The resulting solid was triturated overnight in ethyl acetate. Filtration gave 9.09 g (46%) of (±)-4-((αR*)-α-((2R*, 5S*)-2,5-dimethyl-1-piperazinyl)-3-hydroxybenzyl)-N,N diethylbenzamide as a tan solid. Calc. for C24H33N3O2 0.5 H2O: C, 71.26; H, 8.47; N, 10.39. Found: C, 71.12; H, 8.47; N, 10.49. NMR (300 MHz, CDCl3): δ0.9 (d, J=6 Hz, 3H),1.2 (d and brtr, 9H); 1.5 (t, J=10 Hz, 1H); 2.2 (br m, 1H); 2.5 (m, 1H); 2.6 (d, J=9 Hz, 1H); 2.8 (m, 2H); 3.1-3.5 (br m, 5.3 (s, 1H); 6.6 (d, J=8 Hz, 1H) 6.7 (d, J=8 Hz, 1H); 6.8 (s, 1H); 7.1 (t, J=8 Hz, 1H); 7.2 and 7.3 (AB q, J=8 Hz, 4H), 9.0 (br s, 1H).

Workup

  1. temperatureThe solution was heated
  2. temperatureat reflux for three days
  3. filtrationfiltered through Celite
  4. customThe solvent was removed
  5. customthe residue was purified by chromatography on silica gel with ethanol (0-20%) in dichloromethane containing 1% tdethylamine
  6. customThe solvent was removed
  7. dissolutionthe residue was redissolved in dichloromethane
  8. washwashed with water at pH 8
  9. dry with materialThe organic layer was dried over sodium sulfate
  10. concentrationconcentrated to dryness
  11. customThe resulting solid was triturated overnight in ethyl acetate
  12. filtrationFiltration

Sources & evidence

ORD record
ord-e1cc7830acb4480892cb6cc9bf19f4c0
Source dataset
uspto-grants-1997_08
Patent number
US05658908

Reaction notes

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