Sodium Iodide → 4-((alpha-R)-alpha-((2S,5R)-2,5-Dimethyl-4-(2-fluorobenzyl)-1-piperazinyl)-3-methoxybenzyl)-N,N-diethylbenzamide

HRID 237898

Reaktionsgleichung

Reaktionsgleichung von HRID 237898
[CH3:1][C@H:2]1[CH2:7][NH:6][C@H:5]([CH3:8])[CH2:4][N:3]1[C@H:9]([C:18]1[CH:30]=[CH:29][C:21]([C:22]([N:24]([CH2:27][CH3:28])[CH2:25][CH3:26])=[O:23])=[CH:20][CH:19]=1)[C:10]1[CH:15]=[CH:14][CH:13]=[C:12]([O:16][CH3:17])[CH:11]=1.[F:31][C:32]1[CH:39]=[CH:38][CH:37]=[CH:36][C:33]=1[CH2:34]Br.[I-].[Na+].C(N(CC)CC)C.C(=O)([O-])[O-].[Na+].[Na+].O>>[CH3:1][C@H:2]1[CH2:7][N:6]([CH2:34][C:33]2[CH:36]=[CH:37][CH:38]=[CH:39][C:32]=2[F:31])[C@H:5]([CH3:8])[CH2:4][N:3]1[C@H:9]([C:18]1[CH:19]=[CH:20][C:21]([C:22]([N:24]([CH2:25][CH3:26])[CH2:27][CH3:28])=[O:23])=[CH:29][CH:30]=1)[C:10]1[CH:15]=[CH:14][CH:13]=[C:12]([O:16][CH3:17])[CH:11]=1

Komponenten

6

Edukt 5

HCID 5238Sodium IodideHCID 8471TriethylamineHCID 67968alpha-Bromo-o-fluorotolueneHCID 2735133Sodium Carbonate MonohydrateHCID 105735814-((alpha-R)-alpha-((2S,5R)-2,5-dimethyl-1-piperazinyl)-3-methoxybenzyl)-N,N-diethylbenzamide

Produkt 1

HCID 160487314-((alpha-R)-alpha-((2S,5R)-2,5-Dimethyl-4-(2-fluorobenzyl)-1-piperazinyl)-3-methoxybenzyl)-N,N-diethylbenzamideAusbeute 96,2 %

Versuchsvorschrift

By a procedure essentially identical to that of Example 3, the title compound was prepared from 1.23 g (3.00 mmol) of 4-((alpha-R)-alpha-((2S,5R)-2,5-dimethyl-1-piperazinyl)-3-methoxybenzyl)-N,N-diethylbenzamide, 2-fluorobenzyl bromide (724 μL, 6.0 mmol), sodium iodide (45 mg, 0.30 mmol), and triethylamine (1.51 mL, 10.8 mmol). The crude product was slurried with 1:1 saturated sodium carbonate/water for several hours with manual crushing of suspended solids. Crystalline product was collected by filtration, washed with water and dried to give 1.494 g of 4-((alpha-R)-alpha-((2S,5R)-2,5-dimethyl-4-(2-fluorobenzyl)-1-piperazinyl)-3-methoxybenzyl)-N,N-diethylbenzamide as a white solid. Calc. for C32H40FN3O2 0.1 H2O: C, 73.99; H, 7.80; N, 8.09; F, 3.66. Found C, 73.98; H, 7.86; N, 8.00; F, 3.77. 1H NMR (CDCl3, 300 MHz); δ 1.09 (d, J˜7 Hz, 3H); 1.11 (d, J˜7 Hz, 3H); 1.945 (apparent t, J˜9 Hz, 1H); 2.07 (apparent t, J˜9 Hz, 1H); 2.59 (m, 2H); 2.63 (d, J˜11 Hz, 1H); 2.73 (d, J˜11 Hz, 1H); 3.28 (brd m, 2H); 3.33 (half of ABq, J˜14 Hz, 1H); 3.54 (brd m, 2H); 3.78 (s, 3H); 3.88 (half of ABq, J˜14 Hz, 1H); 5.14 (s, 1H); 6.74 (s, 1H); 6.80 (m, 2H); 7.00 (t, J˜8 Hz, 1H); 7.07 (t, J˜7 Hz, 1H); 7.22 (m, 2H); 7.29 (half of ABq, J˜8 Hz, 2H); 7.37 (t, J˜7 Hz, 1H); 7.47 (half of ABq, J˜8 Hz, 2H).

Aufarbeitung

  1. customwith manual crushing of suspended solids
  2. filtrationCrystalline product was collected by filtration
  3. washwashed with water
  4. customdried

Quellen und Nachweise

ORD-Eintrag
ord-8bb7547412ef4d96ba034c113b90be7a
Quelldatensatz
uspto-grants-2014_02
Patentnummer
US08642599B2

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