4-Fluorophenol → 1,1-Dimethylethyl (2S)-4-({4-[({6-[(4-fluorophenyl)oxy]-2-pyridinyl}carbonyl) (methyl)amino]phenyl}methyl)-2-methyl-1-piperazinecarboxylate

HRID 534792Notes

Reaction equation

HRID 534792 reaction equation
[H-].[Na+].[F:3][C:4]1[CH:9]=[CH:8][C:7]([OH:10])=[CH:6][CH:5]=1.Cl[C:12]1[N:17]=[C:16]([C:18]([N:20]([CH3:42])[C:21]2[CH:26]=[CH:25][C:24]([CH2:27][N:28]3[CH2:33][CH2:32][N:31]([C:34]([O:36][C:37]([CH3:40])([CH3:39])[CH3:38])=[O:35])[C@@H:30]([CH3:41])[CH2:29]3)=[CH:23][CH:22]=2)=[O:19])[CH:15]=[CH:14][CH:13]=1>CN(C=O)C>[F:3][C:4]1[CH:9]=[CH:8][C:7]([O:10][C:12]2[N:17]=[C:16]([C:18]([N:20]([CH3:42])[C:21]3[CH:26]=[CH:25][C:24]([CH2:27][N:28]4[CH2:33][CH2:32][N:31]([C:34]([O:36][C:37]([CH3:39])([CH3:38])[CH3:40])=[O:35])[C@@H:30]([CH3:41])[CH2:29]4)=[CH:23][CH:22]=3)=[O:19])[CH:15]=[CH:14][CH:13]=2)=[CH:6][CH:5]=1

Participants

5

Reactant 3

HCID 97324-FluorophenolHCID 24758Sodium hydrideHCID 59262188HCID 59262188, compound

Product 1

HCID 592621371,1-Dimethylethyl (2S)-4-({4-[({6-[(4-fluorophenyl)oxy]-2-pyridinyl}carbonyl) (methyl)amino]phenyl}methyl)-2-methyl-1-piperazinecarboxylateYield 46.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
190 °C

Procedure

To sodium hydride (0.0174 g, 60% dispersion in mineral oil, 0.436 mmol) in DMF (4 mL) was added 4-fluorophenol (0.0488 g, 0.436 mmol) and the mixture stirred under an argon atmosphere for 20 minutes. 1,1-Dimethylethyl (2S)-4-({4-[[(6-chloro-2-pyridinyl)carbonyl](methyl)amino]phenyl}methyl)-2-methyl-1-piperazinecarboxylate (D107) (0.100 g, 0.218 mmol) was added and the reaction mixture was heated in a microwave at 190° C. for 1.5 h. The reaction mixture was concentrated and the residue partitioned between DCM and water. The aqueous layer was further extracted with DCM and the combined organics were dried over Na2SO4 and concentrated to give a yellow oil which was purified by column chromatography to give the title compound as a colourless oil (0.0539 g). MS (ES): MH+ 535.4.

Workup

  1. concentrationThe reaction mixture was concentrated
  2. customthe residue partitioned between DCM and water
  3. extractionThe aqueous layer was further extracted with DCM
  4. dry with materialthe combined organics were dried over Na2SO4
  5. concentrationconcentrated
  6. customto give a yellow oil which
  7. customwas purified by column chromatography

Sources & evidence

ORD record
ord-2054a82878d74dcf897aef1d1b933503
Source dataset
uspto-grants-2014_10
Patent number
US08853218B2

Reaction notes

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