4-Methylmorpholine → 2-{4-[2-(2,4-Dichloro-phenyl)-1-hydroxy-1-trifluoromethyl-propyl]-pyridin-2-yloxy}-1-morpholin-4-yl-ethanone

HRID 333821Notes

Reaction equation

HRID 333821 reaction equation
[Cl:1][C:2]1[CH:7]=[C:6]([Cl:8])[CH:5]=[CH:4][C:3]=1[CH:9]([CH3:27])[C:10]([C:16]1[CH:21]=[CH:20][N:19]=[C:18]([O:22][CH2:23][C:24]([OH:26])=O)[CH:17]=1)([OH:15])[C:11]([F:14])([F:13])[F:12].[NH:28]1[CH2:33][CH2:32][O:31][CH2:30][CH2:29]1.CN1CCOCC1.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C.O>[Cl:1][C:2]1[CH:7]=[C:6]([Cl:8])[CH:5]=[CH:4][C:3]=1[CH:9]([CH3:27])[C:10]([C:16]1[CH:21]=[CH:20][N:19]=[C:18]([O:22][CH2:23][C:24]([N:28]2[CH2:33][CH2:32][O:31][CH2:30][CH2:29]2)=[O:26])[CH:17]=1)([OH:15])[C:11]([F:14])([F:12])[F:13]

Participants

7

Reactant 4

HCID 79724-MethylmorpholineHCID 8083MorpholineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 25254148HCID 25254148, compound

Product 1

HCID 574212592-{4-[2-(2,4-Dichloro-phenyl)-1-hydroxy-1-trifluoromethyl-propyl]-pyridin-2-yloxy}-1-morpholin-4-yl-ethanone

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

{4-[2-(2,4-Dichloro-phenyl)-1-hydroxy-1-trifluoromethyl-propyl]-pyridin-2-yloxy}-acetic acid (180 mg) and morpholin (0.04 mL) in DMF (6 mL), were treated with 4-methyl-morpholine (0.140 mL) and HBTU (241 mg). The reaction mixture was stirred at r.t. for 17 h. The reaction mixture was diluted with water (50 mL) and extracted twice with ethyl acetate. The combined organic phases were washed with brine, dried over MgSO4 and concentrated in vacuo. The residue was purified by flash chromatography (10 g silica gel, ethyl acetate/heptane 70:30) to give the title compound as white solid (134 mg). MS (m/e)=492.9 (MH+).

Workup

  1. extractionextracted twice with ethyl acetate
  2. washThe combined organic phases were washed with brine
  3. dry with materialdried over MgSO4
  4. concentrationconcentrated in vacuo
  5. customThe residue was purified by flash chromatography (10 g silica gel, ethyl acetate/heptane 70:30)

Sources & evidence

ORD record
ord-4f54d03814334db6ad0ce450aefaff21
Source dataset
uspto-grants-2014_11
Patent number
US08883786B2

Reaction notes

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