Potassium Iodide → (2R)-1-[3,5-bis(trifluoromethyl)benzoyl]-4-[4-(3,3-dimethylmorpholino)-2-butynyl]-2-(2-naphthylmethyl)piperazine dihydrochloride

HRID 584187Notes

Reaction equation

HRID 584187 reaction equation
[F:1][C:2]([F:38])([F:37])[C:3]1[CH:4]=[C:5]([CH:30]=[C:31]([C:33]([F:36])([F:35])[F:34])[CH:32]=1)[C:6]([N:8]1[CH2:13][CH2:12][N:11]([CH2:14][C:15]#[C:16][CH2:17][Cl:18])[CH2:10][C@H:9]1[CH2:19][C:20]1[CH:29]=[CH:28][C:27]2[C:22](=[CH:23][CH:24]=[CH:25][CH:26]=2)[CH:21]=1)=[O:7].[ClH:39].[CH3:40][C:41]1([CH3:47])[CH2:46][O:45][CH2:44][CH2:43][NH:42]1.C(=O)([O-])[O-].[K+].[K+].[I-].[K+]>CN(C)C=O>[ClH:18].[ClH:39].[F:1][C:2]([F:38])([F:37])[C:3]1[CH:4]=[C:5]([CH:30]=[C:31]([C:33]([F:36])([F:35])[F:34])[CH:32]=1)[C:6]([N:8]1[CH2:13][CH2:12][N:11]([CH2:14][C:15]#[C:16][CH2:17][N:42]2[CH2:43][CH2:44][O:45][CH2:46][C:41]2([CH3:47])[CH3:40])[CH2:10][C@H:9]1[CH2:19][C:20]1[CH:29]=[CH:28][C:27]2[C:22](=[CH:23][CH:24]=[CH:25][CH:26]=2)[CH:21]=1)=[O:7]

Participants

6

Reactant 4

HCID 4875Potassium IodideHCID 11430Potassium CarbonateHCID 223428633,3-Dimethylmorpholine hydrochlorideHCID 53862488(2R)-1-[3,5-bis(trifluoromethyl)benzoyl]-4-(4-chloro-2-butynyl)-2-(2-naphthylmethyl)piperazine

Product 1

HCID 86588512(2R)-1-[3,5-bis(trifluoromethyl)benzoyl]-4-[4-(3,3-dimethylmorpholino)-2-butynyl]-2-(2-naphthylmethyl)piperazine dihydrochlorideYield 47.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A mixture of (2R)-1-[3,5-bis(trifluoromethyl)benzoyl]-4-(4-chloro-2-butynyl)-2-(2-naphthylmethyl)piperazine (600 mg), 3,3-dimethylmorpholine hydrochloride (197 mg) and potassium carbonate (420 mg) in N,N-dimethylformamide (10 ml) was stirred at room temperature in the presence of potassium iodide (10 mg) for 2 days. The reaction mixture was partitioned between ethyl acetate (50 ml) and water (100 ml) and the organic layer was separated, washed with brine and dried over magnesium sulfate. After evaporation of the solvent, the residue was purified by column chromatography on silica gel using a mixture of ethyl acetate-hexane (10:1). The obtained product was dissolved in ethyl acetate and treated with 4N hydrogen chloride in ethyl acetate to give (2R)-1-[3,5-bis(trifluoromethyl)benzoyl]-4-[4-(3,3-dimethylmorpholino)-2-butynyl]-2-(2-naphthylmethyl)piperazine dihydrochloride (360 mg).

Workup

  1. customThe reaction mixture was partitioned between ethyl acetate (50 ml) and water (100 ml)
  2. customthe organic layer was separated
  3. washwashed with brine
  4. dry with materialdried over magnesium sulfate
  5. customAfter evaporation of the solvent
  6. customthe residue was purified by column chromatography on silica gel using
  7. additiona mixture of ethyl acetate-hexane (10:1)
  8. dissolutionThe obtained product was dissolved in ethyl acetate
  9. additiontreated with 4N hydrogen chloride in ethyl acetate

Sources & evidence

ORD record
ord-c9ab36f661554cd1b72107d65c27e7c0
Source dataset
uspto-grants-2005_08
Patent number
US06924278B2

Reaction notes

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