Triethylamine → (2R)-1-[3,5-bis(trifluoromethyl) benzoyl]-2-(3,4-dimethylbenzyl)-4-[3-(3,3-dimethylmorpholino imino)propyl]piperazine dihydrochloride

HRID 584202Notes

Reaction equation

HRID 584202 reaction equation
[ClH:1].Cl.[NH2:3][N:4]1[CH2:9][CH2:8][O:7][CH2:6][C:5]1([CH3:11])[CH3:10].C(N(CC)CC)C.[F:19][C:20]([F:53])([F:52])[C:21]1[CH:22]=[C:23]([CH:45]=[C:46]([C:48]([F:51])([F:50])[F:49])[CH:47]=1)[C:24]([N:26]1[CH2:31][CH2:30][N:29]([CH2:32][CH2:33][CH:34]=O)[CH2:28][C@H:27]1[CH2:36][C:37]1[CH:42]=[CH:41][C:40]([CH3:43])=[C:39]([CH3:44])[CH:38]=1)=[O:25]>ClCCl>[ClH:1].[ClH:1].[F:53][C:20]([F:19])([F:52])[C:21]1[CH:22]=[C:23]([CH:45]=[C:46]([C:48]([F:49])([F:50])[F:51])[CH:47]=1)[C:24]([N:26]1[CH2:31][CH2:30][N:29]([CH2:32][CH2:33][CH:34]=[N:3][N:4]2[CH2:9][CH2:8][O:7][CH2:6][C:5]2([CH3:11])[CH3:10])[CH2:28][C@H:27]1[CH2:36][C:37]1[CH:42]=[CH:41][C:40]([CH3:43])=[C:39]([CH3:44])[CH:38]=1)=[O:25]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 223426544-Amino-3,3-dimethylmorpholine dihydrochlorideHCID 86588518(2R)-1-[3,5-bis(trifluoromethyl)benzoyl]-2-(3,4-dimethylbenzyl)-4-(2-formylethyl)piperazine

Product 1

HCID 86596441(2R)-1-[3,5-bis(trifluoromethyl) benzoyl]-2-(3,4-dimethylbenzyl)-4-[3-(3,3-dimethylmorpholino imino)propyl]piperazine dihydrochlorideYield 59.4%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a stirred mixture of 4-amino-3,3-dimethylmorpholine dihydrochloride (122 mg) in dichloromethane (5 ml) was added triethylamine (61 mg) at ice bath temperature. A solution of (2R)-1-[3,5-bis(trifluoromethyl)benzoyl]-2-(3,4-dimethyl benzyl)-4-(2-formylethyl)piperazine (150 mg) in dichloromethane (2 ml) was added and the resulting mixture was stirred at room temperature. After 30 minutes, the reaction mixture was concentrated under reduced pressure. The resulting residue was chromatographed on a silica gel using a mixture of hexane and ethyl acetate as eluent and the desired product was treated with 4N hydrogen chloride in ethyl acetate to give (2R)-1-[3,5-bis(trifluoromethyl) benzoyl]-2-(3,4-dimethylbenzyl)-4-[3-(3,3-dimethylmorpholino-imino)propyl]piperazine dihydrochloride (122 mg).

Workup

  1. concentrationthe reaction mixture was concentrated under reduced pressure
  2. customThe resulting residue was chromatographed on a silica gel using
  3. additiona mixture of hexane and ethyl acetate as eluent
  4. additionthe desired product was treated with 4N hydrogen chloride in ethyl acetate

Sources & evidence

ORD record
ord-d5d7346f129145a9a8e5b2e359ab0dbf
Source dataset
uspto-grants-2005_08
Patent number
US06924278B2

Reaction notes

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