Acetone, oxime → 4-((2'R,6'S)-3,3''-dimethyl-3',4',5',6'-tetrahydro-2'H-[2,2'; 6',2'']terpyridin-1'-ylmethyl)-2-isopropylideneaminooxy-benzonitrile

HRID 1784192Notes

Reaction equation

HRID 1784192 reaction equation
CC(C)([O-])C.[K+].[CH3:7][C:8](=[N:10][OH:11])[CH3:9].[CH3:12][C:13]1[C:14]([C@H:19]2[CH2:24][CH2:23][CH2:22][C@@H:21]([C:25]3[C:30]([CH3:31])=[CH:29][CH:28]=[CH:27][N:26]=3)[N:20]2[CH2:32][C:33]2[CH:40]=[CH:39][C:36]([C:37]#[N:38])=[C:35](F)[CH:34]=2)=[N:15][CH:16]=[CH:17][CH:18]=1>CN(C=O)C>[CH3:31][C:30]1[C:25]([C@H:21]2[CH2:22][CH2:23][CH2:24][C@@H:19]([C:14]3[C:13]([CH3:12])=[CH:18][CH:17]=[CH:16][N:15]=3)[N:20]2[CH2:32][C:33]2[CH:34]=[CH:35][C:36]([C:37]#[N:38])=[C:39]([O:11][N:10]=[C:8]([CH3:9])[CH3:7])[CH:40]=2)=[N:26][CH:27]=[CH:28][CH:29]=1

Participants

5

Reactant 3

HCID 67180Acetone, oximeHCID 23665647Potassium tert-butoxideHCID 674219844-((2'R,6'S)-3,3''-dimethyl-3',4',5',6'-tetrahydro-2'H-[2,2'; 6',2'']terpyridin-1'-ylmethyl)-2-fluoro-benzonitrile

Product 1

HCID 865971254-((2'R,6'S)-3,3''-dimethyl-3',4',5',6'-tetrahydro-2'H-[2,2'; 6',2'']terpyridin-1'-ylmethyl)-2-isopropylideneaminooxy-benzonitrileYield 69%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

To a solution of potassium tert-butoxide (0.140 g, 1.25 mmol) in dry DMF (5 mL) was added acetone oxime (0.0877 g, 1.20 mmol), and the mixture was stirred for 30 min. A solution of 4-((2′R,6′S)-3,3″-dimethyl-3′,4′,5′,6′-tetrahydro-2′H-[2,2′;6′,2″]terpyridin-1′-ylmethyl)-2-fluoro-benzonitrile (0.400 g, 1.00 mmol) in dry DMF (5 mL) was then added, and the mixture was stirred overnight. The solvent was then removed by evaporation under vacuum, and saturated aqueous NaHCO3 (10 mL) was added. The mixture was extracted with EtOAc (3×30 mL), and the extract was dried over Na2SO4. After filtration the solvent was removed by evaporation under vacuum, and the residue was purified on silica gel column (1000:25:1 CH2Cl2/CH3OH/NH4OH), affording 4-((2′R,6′S)-3,3″-dimethyl-3′,4′,5′,6′-tetrahydro-2′H-[2,2′;6′,2″]terpyridin-1′-ylmethyl)-2-isopropylideneaminooxy-benzonitrile as a pale yellow solid (0.311 g, 69%). 1H NMR (CDCl3) δ 1.65-1.75 (m, 3H), 2.06 (s, 3H), 2.07 (s, 3H), 2.09-2.14 (m, 1H), 2.20-2.40 (m, 2H), 2.45 (s, 6H), 3.58 (s, 2H), 4.19 (s, 1H), 4.23 (s, 1H), 6.14 (d, 1H, J=7.8 Hz), 6.68 (s, 1H), 6.91-6.96 (m, 3H), 7.22 (d, 2H, J=7.2 Hz), 8.35 (d, 2H, J=3.9 Hz).

Workup

  1. stirringthe mixture was stirred overnight
  2. customThe solvent was then removed by evaporation under vacuum, and saturated aqueous NaHCO3 (10 mL)
  3. additionwas added
  4. extractionThe mixture was extracted with EtOAc (3×30 mL)
  5. dry with materialthe extract was dried over Na2SO4
  6. filtrationAfter filtration the solvent
  7. customwas removed by evaporation under vacuum
  8. customthe residue was purified on silica gel column (1000:25:1 CH2Cl2/CH3OH/NH4OH)

Sources & evidence

ORD record
ord-41ffeaac47594f33aa948715cc781f89
Source dataset
uspto-grants-2009_03
Patent number
US07501518B2

Reaction notes

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