Sodium Iodide → (cis)-1-((4-Chlorophenoxy)methyl)carbonyl-3,5-dimethyl-4-(4-fluorobenzyl)piperazine

HRID 488397Notes

Reaction equation

HRID 488397 reaction equation
[Cl:1][C:2]1[CH:19]=[CH:18][C:5]([O:6][CH2:7][C:8]([N:10]2[CH2:15][C@H:14]([CH3:16])[NH:13][C@H:12]([CH3:17])[CH2:11]2)=[O:9])=[CH:4][CH:3]=1.[F:20][C:21]1[CH:28]=[CH:27][C:24]([CH2:25]Br)=[CH:23][CH:22]=1.C(N(C(C)C)CC)(C)C.[I-].[Na+]>C1COCC1.CCOCC>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([O:6][CH2:7][C:8]([N:10]2[CH2:11][C@H:12]([CH3:17])[N:13]([CH2:25][C:24]3[CH:27]=[CH:28][C:21]([F:20])=[CH:22][CH:23]=3)[C@H:14]([CH3:16])[CH2:15]2)=[O:9])=[CH:18][CH:19]=1

Participants

7

Reactant 4

HCID 5238Sodium IodideHCID 680214-Fluorobenzyl bromideHCID 81531DiisopropylethylamineHCID 54020178(cis)-1-((4-Chlorophenoxy)methyl)carbonyl-3,5-dimethylpiperazine

Product 1

HCID 54360860(cis)-1-((4-Chlorophenoxy)methyl)carbonyl-3,5-dimethyl-4-(4-fluorobenzyl)piperazineYield 61.3%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of (cis)-1-((4-chlorophenoxy)methyl)carbonyl-3,5-dimethylpiperazine (0.20 g, 0.71 mmol) in anhydrous THF (2 mL) was added 4-fluorobenzyl-bromide (0.11 mL, 0.85 mmol), diisopropylethylamine (0.15 mL, 0.85 mmol) and sodium iodide (0.042 g, 0.28 mmol). The resultant mixture was stirred at ambient temperature for 2 days. At that time the mixture was poured into ether and washed with 5% aqueous NaHCO3 solution, then brine. The organic layer was dried over MgSO4, filtered, and concentrated in vacuo to afford a yellow oil. Purification by flash column chromatography on silica gel afforded 0.17 g of (cis)-1-((4-chlorophenoxy)methyl)carbonyl-3,5-dimethyl-4-(4-fluorobenzyl)piperazine as a pink oil; which was converted to its hydrochoride salt; NMR (CDCl3) 7.6 (m, 2), 7.3 (m, 4), 7.0-6.8 (m, 2), 5.0-2.8 (m, 10), 1.5-1.3 (m, 6) ppm.

Workup

  1. washwashed with 5% aqueous NaHCO3 solution
  2. dry with materialThe organic layer was dried over MgSO4
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo
  5. customto afford a yellow oil
  6. customPurification by flash column chromatography on silica gel

Sources & evidence

ORD record
ord-d2d9ae43f9ed418b80816bc85bc291b9
Source dataset
uspto-grants-2005_12
Patent number
US06972290B2

Reaction notes

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