Potassium Carbonate → (2R)-1-[3,5-bis(trifluoromethyl)benzoyl]-2-(3,4-dimethylbenzyl)-4-[(E)-4-(3,3-dimethylmorpholino)-2-butenyl]piperazine dihydrochloride

HRID 2288213Notes

Reaction equation

HRID 2288213 reaction equation
[F:1][C:2]([F:36])([F:35])[C:3]1[CH:4]=[C:5]([CH:28]=[C:29]([C:31]([F:34])([F:33])[F:32])[CH:30]=1)[C:6]([N:8]1[CH2:13][CH2:12][N:11]([CH2:14]/[CH:15]=[CH:16]/[CH2:17][Cl:18])[CH2:10][C@H:9]1[CH2:19][C:20]1[CH:25]=[CH:24][C:23]([CH3:26])=[C:22]([CH3:27])[CH:21]=1)=[O:7].[ClH:37].[CH3:38][C:39]1([CH3:45])[CH2:44][O:43][CH2:42][CH2:41][NH:40]1.C(=O)([O-])[O-].[K+].[K+]>C(#N)C>[ClH:18].[ClH:37].[F:1][C:2]([F:36])([F:35])[C:3]1[CH:4]=[C:5]([CH:28]=[C:29]([C:31]([F:34])([F:33])[F:32])[CH:30]=1)[C:6]([N:8]1[CH2:13][CH2:12][N:11]([CH2:14]/[CH:15]=[CH:16]/[CH2:17][N:40]2[CH2:41][CH2:42][O:43][CH2:44][C:39]2([CH3:45])[CH3:38])[CH2:10][C@H:9]1[CH2:19][C:20]1[CH:25]=[CH:24][C:23]([CH3:26])=[C:22]([CH3:27])[CH:21]=1)=[O:7]

Participants

5

Reactant 3

HCID 11430Potassium Carbonate2×HCID 223428633,3-Dimethylmorpholine hydrochloride2×HCID 86584247(2R)-1-[3,5-bis(trifluoromethyl)benzoyl]-2-(3,4-dimethylbenzyl)-4-[(E)-4-chloro-2-butenyl]piperazine

Product 1

HCID 86584245(2R)-1-[3,5-bis(trifluoromethyl)benzoyl]-2-(3,4-dimethylbenzyl)-4-[(E)-4-(3,3-dimethylmorpholino)-2-butenyl]piperazine dihydrochlorideYield 64%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

A mixture of (2R)-1-[3,5-bis(trifluoromethyl)benzoyl]-4-[(E)-4-chloro-2-butenyl]-2-(3,4-dimethylbenzyl)piperazine (450 mg), 3,3-dimethylmorpholine hydrochloride (130 mg) and powdered potassium carbonate (350 mg) in dry acetonitrile (5 ml) was heated at reflux temperature for 3 hours. Additional potassium carbonate (350 mg) and 3,3-dimethylmorpholine hydrochloride (130 mg) were added and then the resulting mixture was further heated at reflux temperature. After 6 hours, the reaction mixture was cooled and then filtered. The filtrate was concentrated under reduced pressure and the resulting residue was purified by column chromatography on silica gel using a mixture of dichloromethane and methanol (50:1). The obtained product was dissolved in ethyl acetate and treated with 4N hydrogen chloride in ethyl acetate solution to give (2R)-1-[3,5-bis(trifluoromethyl)benzoyl]-2-(3,4-dimethylbenzyl)-4-[(E)-4-(3,3-dimethylmorpholino)-2-butenyl]piperazine dihydrochloride (370 mg).

Workup

  1. temperaturewas heated
  2. temperatureat reflux temperature for 3 hours
  3. temperaturethe resulting mixture was further heated
  4. temperatureat reflux temperature
  5. temperaturethe reaction mixture was cooled
  6. filtrationfiltered
  7. concentrationThe filtrate was concentrated under reduced pressure
  8. customthe resulting residue was purified by column chromatography on silica gel using
  9. additiona mixture of dichloromethane and methanol (50:1)
  10. dissolutionThe obtained product was dissolved in ethyl acetate
  11. additiontreated with 4N hydrogen chloride in ethyl acetate solution

Sources & evidence

ORD record
ord-63fb8c5de05c4ac3925b8a93630362d5
Source dataset
uspto-grants-2000_07
Patent number
US06087357

Reaction notes

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