Water → (2R)-1-[3,5-bis (trifluoromethyl)benzoyl]-4-[4-(cis-2,6-dimethylmorpholino)-2-butynyl]-2-(2-naphthylmethyl)piperazine dihydrochloride

HRID 584192Notes

Reaction equation

HRID 584192 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].[CH3:39][C@H:40]1[O:45][C@@H:44]([CH3:46])[CH2:43][NH:42][CH2:41]1.C(=O)([O-])[O-].[K+].[K+].O>CN(C)C=O>[ClH:18].[ClH:18].[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[CH2:41][C@@H:40]([CH3:39])[O:45][C@@H:44]([CH3:46])[CH2:43]2)[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 962WaterHCID 11430Potassium CarbonateHCID 6415002,6-Dimethylmorpholine, cis-HCID 53862488(2R)-1-[3,5-bis(trifluoromethyl)benzoyl]-4-(4-chloro-2-butynyl)-2-(2-naphthylmethyl)piperazine

Product 1

HCID 86596430(2R)-1-[3,5-bis (trifluoromethyl)benzoyl]-4-[4-(cis-2,6-dimethylmorpholino)-2-butynyl]-2-(2-naphthylmethyl)piperazine dihydrochlorideYield 88.9%

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 (300 mg), cis-2,6-dimethylmorpholine (94 mg) and powdered potassium carbonate (210 mg) in dry N,N-dimethylformamide (5 ml) was stirred at room temperature overnight. The reaction mixture was poured into water (50 ml) and extracted with ethyl acetate. The extract was washed with brine and dried over magnesium sulfate. After evaporation of the solvent, the obtained residue was purified by column chromatography on silica gel using a mixture of ethyl acetate and hexane (4:1) as eluent. 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-(cis-2,6-dimethylmorpholino)-2-butynyl]-2-(2-naphthylmethyl)piperazine dihydrochloride (170 mg).

Workup

  1. extractionextracted with ethyl acetate
  2. washThe extract was washed with brine
  3. dry with materialdried over magnesium sulfate
  4. customAfter evaporation of the solvent
  5. customthe obtained residue was purified by column chromatography on silica gel using
  6. additiona mixture of ethyl acetate and hexane (4:1) as eluent
  7. dissolutionThe obtained product was dissolved in ethyl acetate
  8. additiontreated with 4N hydrogen chloride in ethyl acetate

Sources & evidence

ORD record
ord-b6ab0615469c407ab89ed4810ca0c561
Source dataset
uspto-grants-2005_08
Patent number
US06924278B2

Reaction notes

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