Hydrochloric Acid → 1-Phenoxy-2,2,6,6-tetramethylpiperidine

HRID 1369344Notes

Reaction equation

HRID 1369344 reaction equation
Cl.N[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.N([O-])=O.[Na+].[OH:13][N:14]1[C:19]([CH3:21])([CH3:20])[CH2:18][CH2:17][CH2:16][C:15]1([CH3:23])[CH3:22]>O.N1C=CC=CC=1.[Cu](F)F>[O:13]([N:14]1[C:19]([CH3:21])([CH3:20])[CH2:18][CH2:17][CH2:16][C:15]1([CH3:23])[CH3:22])[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 6115AnilineHCID 5499762,2,6,6-Tetramethylpiperidin-1-olHCID 23668193Sodium Nitrite

Product 1

HCID 132131751-Phenoxy-2,2,6,6-tetramethylpiperidine

Reagents, catalysts & solvents 3

HCID 522688Copper fluorideCatalystHCID 962WaterSolvent2×HCID 1049PyridineSolvent

Conditions

Temperature
70 °C

Procedure

Into a solution of 5 g of water and 15.3 g (150 mmol) of concentrated hydrochloric acid is added dropwise 4.60 g (50 mmol) of aniline. The temperature of the reaction mixture during the addition step is kept under 40° C. After the addition is complete, the reaction mixture is heated to 70° C. for one hour. The reaction mixture is then cooled to 0° to 5° C. followed by a dropwise addition of an aqueous solution of 3.45 g (50 mmol) of sodium nitrite in 10 mL of water. The addition time is 20 minutes while the reaction temperature is maintained at 0° to 5° C. The reaction mixture is transferred to a cold-jacketed addition funnel and is then added dropwise into a solution of 3.9 g (25 mmol) of 1-oxyl-2,2,6,6-tetramethylpiperidine, 25 mg (0.25 mmol) of copper(II) fluoride in 120 mL of pyridine at 70° C. Evolution of nitrogen is observed during the addition. After the addition is complete, the reaction mixture is kept at 70° C. for another 30 minutes followed by cooling to ambient temperature. The reaction mixture is concentrated to a thick oil. The crude product is purified by vacuum flash chromatography (heptane) to give 3.97 g of the title as a colorless oil in 68.4% yield.

Workup

  1. additionThe temperature of the reaction mixture during the addition step
  2. customis kept under 40° C
  3. additionAfter the addition
  4. temperatureThe reaction mixture is then cooled to 0° to 5° C.
  5. temperatureis maintained at 0° to 5° C
  6. customThe reaction mixture is transferred to a cold-jacketed addition funnel
  7. additionEvolution of nitrogen is observed during the addition
  8. additionAfter the addition
  9. waitthe reaction mixture is kept at 70° C. for another 30 minutes
  10. temperatureby cooling to ambient temperature
  11. concentrationThe reaction mixture is concentrated to a thick oil
  12. customThe crude product is purified by vacuum flash chromatography (heptane)
  13. customto give 3.97 g of the title as a colorless oil in 68.4% yield

Sources & evidence

ORD record
ord-2f51f3a079884f309520d459f40e763c
Source dataset
uspto-grants-2003_06
Patent number
US06579328B2

Reaction notes

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