Acetic Anhydride → (+/-)-4-((alphaR*)-3-acetoxy-alpha-((2S*,5R*)-4-allyl-2,5-dimethyl-1-piperazinyl)benzyl)-N,N-diethylbenzamide

HRID 1460089Notes

Reaction equation

HRID 1460089 reaction equation
[CH2:1]([N:4]1[C@H:9]([CH3:10])[CH2:8][N:7]([C@H:11]([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)[C:12]2[CH:17]=[CH:16][CH:15]=[C:14]([OH:18])[CH:13]=2)[C@@H:6]([CH3:32])[CH2:5]1)[CH:2]=[CH2:3].[C:33](OC(=O)C)(=[O:35])[CH3:34].C(N(CC)CC)C>ClCCl>[C:33]([O:18][C:14]1[CH:13]=[C:12]([CH:17]=[CH:16][CH:15]=1)[C@@H:11]([C:19]1[CH:20]=[CH:21][C:22]([C:23]([N:25]([CH2:26][CH3:27])[CH2:28][CH3:29])=[O:24])=[CH:30][CH:31]=1)[N:7]1[CH2:8][C@@H:9]([CH3:10])[N:4]([CH2:1][CH:2]=[CH2:3])[CH2:5][C@@H:6]1[CH3:32])(=[O:35])[CH3:34]

Participants

5

Reactant 3

HCID 7918Acetic AnhydrideHCID 8471TriethylamineHCID 119029rel-4-((R)-((2S,5R)-2,5-Dimethyl-4-(2-propen-1-yl)-1-piperazinyl)(3-hydroxyphenyl)methyl)-N,N-diethylbenzamide

Product 1

HCID 57022607(+/-)-4-((alphaR*)-3-acetoxy-alpha-((2S*,5R*)-4-allyl-2,5-dimethyl-1-piperazinyl)benzyl)-N,N-diethylbenzamideYield 71%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of (±)-4-((αR*)-α-((2S*,5R*)-4-allyl-2,5-dimethyl-1-piperazinyl)-3-hydroxybenzyl)-N,N-diethylbenzamide (1.2 g, 2.8 mmol, Example 6), acetic anhydride (0.40 mL, 4.2 mmol), and triethylamine (0.80 mL, 5.6 mmol) in 30 mL of dichloromethane was stirred overnight under nitrogen. The solution was washed twice with 15 mL of 5% sodium bicarbonate, dried over sodium sulfate and the solvent removed. The product was purified by chromatography on silica gel with ethyl acetate (30-100%) in dichloromethane to give 0.94 g (71%) of (±)-4-((αR*)-3-acetoxy-α-((2S*,5R*)-4-allyl-2,5-dimethyl-1-piperazinyl)benzyl)-N,N-diethylbenzamide as a white foam. NMR (200 MHz, DMSO-d6): δ 0.9 (d, J=6 Hz, 3H); 1.1 (d, J=6 Hz, 3H); 1.0-1.2 (br m, 6H); 1.75 (dd, J1 =7.5 Hz, J2 =12 Hz, 1H); 2.1 (dd, J1 =8.5 Hz, J2 =12.5 Hz, 1H); 2.2 (s, 3H); 2.4-2.6 (m, 3H); 2.7 (m, 1H); 2.8 (dd, J1 =7.5 Hz, J2 =15 Hz, 1H); 3.1 (dd, J1 =6 Hz, J2 =14 Hz, 1H); 3.1-3.4 (br m, 4H); 5.05 (d, J=15 Hz, 1H); 5.1 (s, 1H); 5.15 (d, 10 Hz, 1H), 5.8 (m, 1H) 7.0 (s, 1H); 7.0 (d, J=8 Hz, 1H); 7.15 (d, J=8 Hz, 1H); 7.25 and 7.4 (ABq, J=8 Hz; 4H); 7.4(t, J=8 Hz, 1H). The amine was dissolved in ethanol and converted to the monohydrochloride salt by titration with ethanolic hydrogen chloride. After the solvent was removed, the salt was dissolved in a minimal amount of dichloromethane and precipitated with diethyl ether. Filtration gave 0.50 g of the hygroscopic salt. Calc for C29H39N3O3HCl H2O: C, 65.46; H, 7.97; N, 7.90; Cl, 6.66. Found: C, 65.43; H, 7.97; N, 8.00; Cl, 6.79.

Workup

  1. washThe solution was washed twice with 15 mL of 5% sodium bicarbonate
  2. dry with materialdried over sodium sulfate
  3. customthe solvent removed
  4. customThe product was purified by chromatography on silica gel with ethyl acetate (30-100%) in dichloromethane

Sources & evidence

ORD record
ord-45a3aee9d72c477c96797e89882b4e45
Source dataset
uspto-grants-1998_12
Patent number
US05854249

Reaction notes

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