4-Methylmorpholine → HCID 57550425, compound

HRID 559368Notes

Reaction equation

HRID 559368 reaction equation
[OH-].[K+].[CH2:3]([O:5][C:6](=O)[CH2:7][CH:8]1[C:13](=[O:14])[N:12]([CH2:15][CH2:16][CH2:17][N:18]2[CH2:23][CH2:22][CH2:21][CH2:20][CH2:19]2)[CH2:11][CH2:10][N:9]1[C:24](=[O:35])/[CH:25]=[CH:26]/[C:27]1[CH:32]=[CH:31][C:30]([Cl:33])=[C:29]([Cl:34])[CH:28]=1)C.[ClH:37].[CH3:38][NH:39][CH3:40].CN1CC[O:45]CC1.F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2N=CC=CC=2N=N1>C(O)C.CN(C)C=O>[Cl:37][CH2:29][Cl:34].[CH3:3][OH:5].[OH-:45].[NH4+:9].[Cl:34][C:29]1[CH:28]=[C:27](/[CH:26]=[CH:25]/[C:24]([N:9]2[CH2:10][CH2:11][N:12]([CH2:15][CH2:16][CH2:17][N:18]3[CH2:19][CH2:20][CH2:21][CH2:22][CH2:23]3)[C:13](=[O:14])[CH:8]2[CH2:7][C:6]([N:39]([CH3:40])[CH3:38])=[O:5])=[O:35])[CH:32]=[CH:31][C:30]=1[Cl:33]

Participants

9

Reactant 5

HCID 79724-MethylmorpholineHCID 10473Dimethylamine, hydrochlorideHCID 14797Potassium HydroxideHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 57550385HCID 57550385, compound

Product 2

HCID 21896990Dichloromethane methanol ammonium hydroxideHCID 57550425HCID 57550425, compoundYield 159.2%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 6228DimethylformamideSolvent

Procedure

Potassium hydroxide solution (2 M in water, 90 μL, 0.18 mmol) was added to a solution of [1-[(E)-3-(3,4-dichloro-phenyl)-acryloyl]-3-oxo-4-(3-piperidin-1-yl-propyl)-piperazin-2-yl]-acetic acid ethyl ester (example 33; 92 mg, 0.18 mmol) in ethanol (1 ml). The reaction mixture was stirred at room temperature for 18 h, then after evaporation potassium [1-[(E)-3-(3,4-dichloro-phenyl)-acryloyl]-3-oxo-4-(3-piperidin-1-yl-propyl)-piperazin-2-yl]-acetate was obtained. This was dissolved in N,N-dimethylformamide (1 ml), then dimethylamine hydrochloride (14 mg, 0.17 mmol), 4-methylmorpholine (81 mg, 0.99 mmol), and O-(7-azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluoro-phosphate (92 mg, 0.24 mmol) were added. The reaction mixture was stirred for 16 h at room temperature, then partitioned between ethyl acetate and water. The organic layer was dried (MgSO4), filtered, and evaporated. Chromatography (SiO2; dichloromethane/methanol/ammonium hydroxide 90:10:0.25) afforded the title compound (73 mg, 79%). Off-white foam, MS (ISP)=509.1 (M+H)+.

Workup

  1. customafter evaporation potassium [1-[(E)-3-(3,4-dichloro-phenyl)-acryloyl]-3-oxo-4-(3-piperidin-1-yl-propyl)-piperazin-2-yl]-acetate
  2. customwas obtained
  3. stirringThe reaction mixture was stirred for 16 h at room temperature
  4. custompartitioned between ethyl acetate and water
  5. dry with materialThe organic layer was dried (MgSO4)
  6. filtrationfiltered
  7. customevaporated

Sources & evidence

ORD record
ord-7ab331dec41d4159bc9f496d27ffaf9b
Source dataset
uspto-grants-2011_11
Patent number
US08063042B2

Reaction notes

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