Potassium Iodide → 1-[3,5-bis(trifluoromethyl)benzoyl]-2-[3-[(2-methoxyethoxy)-methoxy]-4-methylbenzyl]-4-[2-[(3R)-3-methoxymethyl-morpholino]ethyl]piperazine

HRID 1374990Notes

Reaction equation

HRID 1374990 reaction equation
[F:1][C:2]([F:37])([F:36])[C:3]1[CH:4]=[C:5]([CH:29]=[C:30]([C:32]([F:35])([F:34])[F:33])[CH:31]=1)[C:6]([N:8]1[CH2:13][CH2:12][NH:11][CH2:10][CH:9]1[CH2:14][C:15]1[CH:20]=[CH:19][C:18]([CH3:21])=[C:17]([O:22][CH2:23][O:24][CH2:25][CH2:26][O:27][CH3:28])[CH:16]=1)=[O:7].Cl.Cl[CH2:40][CH2:41][N:42]1[CH2:47][CH2:46][O:45][CH2:44][C@H:43]1[CH2:48][O:49][CH3:50].C(=O)([O-])[O-].[K+].[K+].[I-].[K+].C(=O)([O-])O.[Na+]>CN(C)C=O>[F:37][C:2]([F:1])([F:36])[C:3]1[CH:4]=[C:5]([CH:29]=[C:30]([C:32]([F:33])([F:34])[F:35])[CH:31]=1)[C:6]([N:8]1[CH2:13][CH2:12][N:11]([CH2:40][CH2:41][N:42]2[CH2:47][CH2:46][O:45][CH2:44][C@H:43]2[CH2:48][O:49][CH3:50])[CH2:10][CH:9]1[CH2:14][C:15]1[CH:20]=[CH:19][C:18]([CH3:21])=[C:17]([O:22][CH2:23][O:24][CH2:25][CH2:26][O:27][CH3:28])[CH:16]=1)=[O:7]

Participants

7

Reactant 5

HCID 4875Potassium IodideHCID 11430Potassium CarbonateHCID 516892Sodium BicarbonateHCID 179639311-[3,5-Bis(trifluoromethyl)benzoyl]-2-[3-[(2-methoxyethoxy)methoxy]-4-methylbenzyl]piperazineHCID 69331387(3R)-4-(2-chloroethyl)-3-(methoxymethyl)morpholine hydrochloride

Product 1

HCID 545047211-[3,5-bis(trifluoromethyl)benzoyl]-2-[3-[(2-methoxyethoxy)-methoxy]-4-methylbenzyl]-4-[2-[(3R)-3-methoxymethyl-morpholino]ethyl]piperazineYield 79%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
73 °C

Procedure

To a solution of 1-[3,5-bis(trifluoromethyl)benzoyl]-2-[3-[(2-methoxyethoxy)methoxy]-4-methylbenzyl]piperazine (440 mg) in N,N-dimethylformamide (2.2 ml) were added (3R)-4-(2-chloroethyl)-3-(methoxymethyl)morpholine hydrochloride (289 mg), potassium carbonate (434 mg) and potassium iodide (149 mg) at room temperature. The whole was stirred at 73° C. for 2 hours. After being cooled to room temperature, the mixture was poured into ice-water and the aqueous mixture was made alkaline with saturated aqueous sodium hydrogen carbonate solution. The resulting mixture was extracted with ethyl acetate. The extract was washed with brine, dried over sodium sulfate and evaporated under reduced pressure. The residue was purified by column chromatography on silica gel using mixed solvents of dichloromethane and methanol (40:1). The fractions containing the objective compound were collected and evaporated under reduced pressure to give 1-[3,5-bis(trifluoromethyl)benzoyl]-2-[3-[(2-methoxyethoxy)-methoxy]-4-methylbenzyl]-4-[2-[(3R)-3-methoxymethyl-morpholino]ethyl]piperazine (450 mg) as a light yellowish oil.

Workup

  1. temperatureAfter being cooled to room temperature
  2. extractionThe resulting mixture was extracted with ethyl acetate
  3. washThe extract was washed with brine
  4. dry with materialdried over sodium sulfate
  5. customevaporated under reduced pressure
  6. customThe residue was purified by column chromatography on silica gel using
  7. additionmixed solvents of dichloromethane and methanol (40:1)
  8. additionThe fractions containing the objective compound
  9. customwere collected
  10. customevaporated under reduced pressure

Sources & evidence

ORD record
ord-b641469e45e24d8f80159f33649bfb24
Source dataset
uspto-grants-2007_01
Patent number
US07166598B2

Reaction notes

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