Trifluoroacetic acid → HCID 59441736, compound

HRID 1014347Notes

Reaction equation

HRID 1014347 reaction equation
F[C:2]1[CH:7]=[CH:6][C:5]([N+:8]([O-:10])=[O:9])=[C:4]([O:11][CH3:12])[CH:3]=1.[OH:13][CH2:14][CH:15]1[CH2:20][CH2:19][N:18]([C:21](OC(C)(C)C)=O)[CH2:17][CH2:16]1.[H-].[Na+].F[C:31](F)(F)[C:32](O)=O.ICCC.C(=O)([O-])[O-].[K+].[K+]>CN(C=O)C.C(OCC)(=O)C>[CH3:12][O:11][C:4]1[CH:3]=[C:2]([O:13][CH2:14][CH:15]2[CH2:16][CH2:17][N:18]([CH2:21][CH2:31][CH3:32])[CH2:19][CH2:20]2)[CH:7]=[CH:6][C:5]=1[N+:8]([O-:10])=[O:9]

Participants

9

Reactant 6

HCID 6422Trifluoroacetic acidHCID 11430Potassium CarbonateHCID 24758Sodium hydrideHCID 336431-IodopropaneHCID 2764081Tert-butyl 4-(hydroxymethyl)piperidine-1-carboxylateHCID 27792505-Fluoro-2-nitroanisole

Product 1

HCID 59441736HCID 59441736, compoundYield 50.3%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent2×

Procedure

To a solution of 4-fluoro-2-(methyloxy)-1-nitrobenzene (1 g, 5.8 mmol) in 20 mL of anhydrous DMF was added 1,1-dimethylethyl 4-(hydroxymethyl)-1-piperidinecarboxylate (1.5 g, 7.0 mmol). Sodium hydride (60%) (448 mg, 11.68 mmol) was added portionwise. Reaction was stirred at rt for 60 min at which time the reaction was diluted with ethyl acetate and washed with a minimum amount of a saturated solution of sodium bicarbonate, water and a saturated sodium chloride solution, dried over Na2SO4 and filtered. Solvents were removed under reduced pressure and the resulting residue was dissolved in dichloromethane (20 mL) and trifluoroacetic acid (4.5 mL, 58.4 mmol) was added and the mixture was stirred for 30 min at rt. Solvents were removed under reduced pressure and the resulting residue was dissolved in acetonitrile (20 mL) and 1-iodopropane (0.63 mL, 6.4 mmol) and potassium carbonate (2.4 g, 17.52 mmol) were added and stirred at rt for 16 h. Subsequently the reaction mixture was diluted with ethyl acetate and washed with a saturated sodium bicarbonate solution, water and a saturated sodium chloride solution. The organic layer was dried over Na2SO4 and filtered. Solvents were removed under reduced pressure and the residue was purified by SiO2 chromatography to afford 4-({[3-(methyloxy)-4-nitrophenyl]oxy}methyl)-1-propylpiperidine (0.9 g, 2.92 mmol). (ESIMS (M+H)+=309)

Workup

  1. customReaction
  2. washwashed with a minimum amount of a saturated solution of sodium bicarbonate, water
  3. dry with materiala saturated sodium chloride solution, dried over Na2SO4
  4. filtrationfiltered
  5. customSolvents were removed under reduced pressure
  6. dissolutionthe resulting residue was dissolved in dichloromethane (20 mL)
  7. stirringthe mixture was stirred for 30 min at rt
  8. customSolvents were removed under reduced pressure
  9. dissolutionthe resulting residue was dissolved in acetonitrile (20 mL)
  10. stirringstirred at rt for 16 h
  11. washwashed with a saturated sodium bicarbonate solution, water
  12. dry with materialThe organic layer was dried over Na2SO4
  13. filtrationfiltered
  14. customSolvents were removed under reduced pressure
  15. customthe residue was purified by SiO2 chromatography

Sources & evidence

ORD record
ord-67c05b6e142d44d28881584dcdc25ade
Source dataset
uspto-grants-2011_07
Patent number
US07981903B2

Reaction notes

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