Sodium Bicarbonate → (2R)-1-[3,5-bis(trifluoromethyl)benzoyl]-2-(3,4-dimethylbenzyl)-4-[2-[2-(3,3-dimethylmorpholino)ethoxy]ethyl]piperazine dihydrochloride

HRID 584186Notes

Reaction equation

HRID 584186 reaction equation
[ClH:1].[CH3:2][C:3]1([CH3:9])[CH2:8][O:7][CH2:6][CH2:5][NH:4]1.[F:10][C:11]([F:46])([F:45])[C:12]1[CH:13]=[C:14]([CH:38]=[C:39]([C:41]([F:44])([F:43])[F:42])[CH:40]=1)[C:15]([N:17]1[CH2:22][CH2:21][N:20]([CH2:23][CH2:24][O:25][CH2:26][CH:27]=O)[CH2:19][C@H:18]1[CH2:29][C:30]1[CH:35]=[CH:34][C:33]([CH3:36])=[C:32]([CH3:37])[CH:31]=1)=[O:16].C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C(=O)(O)[O-].[Na+]>ClCCl.C(N(CC)CC)C>[ClH:1].[ClH:1].[F:46][C:11]([F:10])([F:45])[C:12]1[CH:13]=[C:14]([CH:38]=[C:39]([C:41]([F:42])([F:43])[F:44])[CH:40]=1)[C:15]([N:17]1[CH2:22][CH2:21][N:20]([CH2:23][CH2:24][O:25][CH2:26][CH2:27][N:4]2[CH2:5][CH2:6][O:7][CH2:8][C:3]2([CH3:9])[CH3:2])[CH2:19][C@H:18]1[CH2:29][C:30]1[CH:35]=[CH:34][C:33]([CH3:36])=[C:32]([CH3:37])[CH:31]=1)=[O:16]

Participants

7

Reactant 4

HCID 516892Sodium BicarbonateHCID 5049666Sodium triacetoxyborohydrideHCID 223428633,3-Dimethylmorpholine hydrochlorideHCID 86588511(2R)-1-[3,5-bis(trifluoromethyl)benzoyl]-2-(3,4-dimethylbenzyl)-4-[2-(formylmethoxy)ethyl]piperazine

Product 1

HCID 86596425(2R)-1-[3,5-bis(trifluoromethyl)benzoyl]-2-(3,4-dimethylbenzyl)-4-[2-[2-(3,3-dimethylmorpholino)ethoxy]ethyl]piperazine dihydrochlorideYield 132.2%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8471TriethylamineSolvent

Procedure

To a stirred mixture of 3,3-dimethylmorpholine hydrochloride (63 mg) and triethylamine (42 mg) in dichloromethane (5 ml) were added (2R)-1-[3,5-bis(trifluoromethyl)benzoyl]-2-(3,4-dimethylbenzyl)-4-[2-(formylmethoxy)ethyl]piperazine (200 mg) and sodium triacetoxyborohydride (120 mg) at room temperature. The resulting mixture was stirred for 1 hour and then treated with aqueous sodium bicarbonate solution. The organic layer was separated and dried over magnesium sulfate. After evaporation of the solvent, the residue was purified by column chromatography on silica gel using dichloromethanemethanol (10:1) as eluent and treated with 4N hydrogen chloride in ethyl acetate to give (2R)-1-[3,5-bis(trifluoromethyl)benzoyl]-2-(3,4-dimethylbenzyl)-4-[2-[2-(3,3-dimethylmorpholino)ethoxy]ethyl]piperazine dihydrochloride (193 mg) as a powder.

Workup

  1. customThe organic layer was separated
  2. dry with materialdried over magnesium sulfate
  3. customAfter evaporation of the solvent
  4. customthe residue was purified by column chromatography on silica gel using dichloromethanemethanol (10:1) as eluent
  5. additiontreated with 4N hydrogen chloride in ethyl acetate

Sources & evidence

ORD record
ord-d30468478fb7410c9bd54d8e93ab40a1
Source dataset
uspto-grants-2005_08
Patent number
US06924278B2

Reaction notes

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