Hydrochloric Acid → 3-[2-(4-{5-[1,1,1,3,3,3-Hexafluoro-2-(4-methoxybenzyloxy)propan-2-yl]-4-propylpyridin-2-yl}piperazin-1-yl)ethyl]-5-[4-(1-methylethoxy)phenyl]-5-methylimidazolidine-2,4-dione

HRID 1038517Notes

Reaction equation

HRID 1038517 reaction equation
[F:1][C:2]([F:37])([F:36])[C:3]([C:18]1[C:19]([CH2:33][CH2:34][CH3:35])=[CH:20][C:21]([N:24]2[CH2:29][CH2:28][N:27]([CH2:30][CH2:31]O)[CH2:26][CH2:25]2)=[N:22][CH:23]=1)([O:8][CH2:9][C:10]1[CH:15]=[CH:14][C:13]([O:16][CH3:17])=[CH:12][CH:11]=1)[C:4]([F:7])([F:6])[F:5].[CH3:38][C:39]1([C:46]2[CH:51]=[CH:50][C:49]([O:52][CH:53]([CH3:55])[CH3:54])=[CH:48][CH:47]=2)[NH:43][C:42](=[O:44])[NH:41][C:40]1=[O:45].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.CCOC(/N=N/C(OCC)=O)=O.Cl>CN(C)C=O.O>[F:36][C:2]([F:1])([F:37])[C:3]([C:18]1[C:19]([CH2:33][CH2:34][CH3:35])=[CH:20][C:21]([N:24]2[CH2:29][CH2:28][N:27]([CH2:30][CH2:31][N:41]3[C:40](=[O:45])[C:39]([C:46]4[CH:51]=[CH:50][C:49]([O:52][CH:53]([CH3:55])[CH3:54])=[CH:48][CH:47]=4)([CH3:38])[NH:43][C:42]3=[O:44])[CH2:26][CH2:25]2)=[N:22][CH:23]=1)([O:8][CH2:9][C:10]1[CH:11]=[CH:12][C:13]([O:16][CH3:17])=[CH:14][CH:15]=1)[C:4]([F:7])([F:6])[F:5]

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 11776TriphenylphosphineHCID 30521535-methyl-5-[4-(propan-2-yloxy)phenyl]imidazolidine-2,4-dioneHCID 5462977Diethyl azodicarboxylateHCID 866471802-(4-{5-[1,1,1,3,3,3-Hexafluoro-2-(4-methoxybenzyloxy)propan-2-yl]-4-propylpyridin-2-yl}piperazin-1-yl)ethanol

Product 1

HCID 866471813-[2-(4-{5-[1,1,1,3,3,3-Hexafluoro-2-(4-methoxybenzyloxy)propan-2-yl]-4-propylpyridin-2-yl}piperazin-1-yl)ethyl]-5-[4-(1-methylethoxy)phenyl]-5-methylimidazolidine-2,4-dioneYield 105%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

2-(4-{5-[1,1,1,3,3,3-Hexafluoro-2-(4-methoxybenzyloxy)propan-2-yl]-4-propylpyridin-2-yl}piperazin-1-yl)ethanol (20 mg, 0.0373 mmol), 5-methyl-5-(4-(1-methylethoxy)phenyl)imidazolidine-2,4-dione (34.3 mg, 0.138 mmol) and triphenylphosphine (34.5 mg, 0.132 mmol) were dried with a vacuum pump, dissolved in N,N-dimethylformamide (3 mL), added DEAD (51 μL, 0.111 mmol) under ice-cold conditions, and the mixture was stirred at room temperature for 1 hour. Under ice-cold conditions, the reaction solution was added water (1.0 mL) and 2N aqueous solution of hydrochloric acid (1.0 mL), extracted with ethyl acetate. The organic layer was washed with brine, dried over anhydrous sodium sulfate, and concentrated in vacuo. The obtained residue was purified by silica-gel column chromatography (hexane/acetone). The title compound (30 mg (yield 99%)) was obtained as a yellow oil.

Workup

  1. extractionextracted with ethyl acetate
  2. washThe organic layer was washed with brine
  3. dry with materialdried over anhydrous sodium sulfate
  4. concentrationconcentrated in vacuo
  5. customThe obtained residue was purified by silica-gel column chromatography (hexane/acetone)

Sources & evidence

ORD record
ord-b9204f3d1d514e98b05c98bc426f8877
Source dataset
uspto-grants-2013_10
Patent number
US08551985B2

Reaction notes

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