Water → HCID 15386113, compound

HRID 741624Notes

Reaction equation

HRID 741624 reaction equation
Cl.C([N:5]1[C@H:10]([CH3:11])[CH2:9][N:8]([C@H:12]([C:20]2[CH:21]=[C:22]([CH:30]=[CH:31][CH:32]=2)[C:23]([N:25]([CH2:28][CH3:29])[CH2:26][CH3:27])=[O:24])[C:13]2[CH:18]=[CH:17][CH:16]=[C:15]([OH:19])[CH:14]=2)[C@@H:7]([CH3:33])[CH2:6]1)C=C.O>[Pd].CO>[CH3:33][C@H:7]1[CH2:6][NH:5][C@H:10]([CH3:11])[CH2:9][N:8]1[C@H:12]([C:20]1[CH:21]=[C:22]([CH:30]=[CH:31][CH:32]=1)[C:23]([N:25]([CH2:28][CH3:29])[CH2:26][CH3:27])=[O:24])[C:13]1[CH:18]=[CH:17][CH:16]=[C:15]([OH:19])[CH:14]=1

Participants

5

Reactant 2

HCID 962WaterHCID 67729061HCID 67729061, compound

Product 1

HCID 15386113HCID 15386113, compoundYield 75%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 887MethanolSolvent

Procedure

A mixture of (+)-3-((αR)-α-((2S,5R)-4-allyl-2,5-dimethyl-1-piperazinyl)-3-hydroxybenzyl)-N,N-diethylbenzamide monohydrochloride (8.22 g, 17.1 mmol. Example 1) and 5.45 g (2.5 mmol) of 5% palladium on charcoal in 160 ml of methanol:water/3:1 was heated at reflux for 20 hours. The reaction mixture was filtered through Celite under nitrogen and the filtrate was evaporated. The residue was diluted with water and the pH was adjusted to 8 with aqueous 1M sodium hydroxide. The mixture was extracted with ethyl acetate, dried over sodium sulfate, and evaporated to give 5.05 g (75%) of (+)-3-((αR)-α-((2S,5R)-2,5-dimethyl-1-piperazinyl)-3-hydroxybenzyl)-N,N-diethyl-benzamide as a light yellow solid. NMR (DMSO-d6, 200 MHz): δ1.1 (m, 12H); 2.0 (m, 1H); 2.6-2.9 (m, 3H); 3.0-3.5 (m, 7H); 5.25 (s, 1H); 6.7 (m, 3H); 7.2 (m, 3H); 7.4 (m, 2H); 9.5 (s, 1H). [α]D20 =+11.9° (abs ethanol, c=2.3). Titration of 0.20 g of product with ethanolic hydrogen chloride in ethanol solution to pH 3.5 and precipitation from dichloromethane with diethyl ether gave 0.103 g (47% recovery) of the monohydrochloride salt as an off-white solid. Calc. for C24H33N3O2HCl 0.75 H2O: C, 64.70; H, 8.03; N, 9.43; Cl, 7.96. Found: C, 64.97; H, 7.97; N, 9.38; Cl, 8.04. Mass spectrum (CI--CH4) m/e 396 (M+1, 38%); 282 (39%); 115 (100%).

Workup

  1. temperatureat reflux for 20 hours
  2. filtrationThe reaction mixture was filtered through Celite under nitrogen
  3. customthe filtrate was evaporated
  4. additionThe residue was diluted with water
  5. extractionThe mixture was extracted with ethyl acetate
  6. dry with materialdried over sodium sulfate
  7. customevaporated

Sources & evidence

ORD record
ord-ffd32b7903ca4e5c8ce0da40821d44e5
Source dataset
uspto-grants-1996_09
Patent number
US05552404

Reaction notes

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