Hydroxylamine → 4-Benzoyloxy-1-ethoxy-2,2,6,6-tetramethylpiperidine

HRID 1493395Notes

Reaction equation

HRID 1493395 reaction equation
[C:1]([O:9][CH:10]1[CH2:15][C:14]([CH3:17])([CH3:16])[N:13]([OH:18])[C:12]([CH3:20])([CH3:19])[CH2:11]1)(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.S([O-])([O-])(=O)=O.[Mg+2].[CH2:27](I)[CH3:28].NO.[H-].[Na+]>[Pd].CS(C)=O.O1CCCC1.O>[C:1]([O:9][CH:10]1[CH2:11][C:12]([CH3:20])([CH3:19])[N:13]([O:18][CH2:27][CH3:28])[C:14]([CH3:16])([CH3:17])[CH2:15]1)(=[O:8])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

10

Reactant 5

HCID 787Hydroxylamine2×HCID 6340IodoethaneHCID 24083Sulfuric acid magnesium salt (1:1)HCID 24758Sodium hydrideHCID 6881781-Hydroxy-4-benzoyloxy-2,2,6,6-tetramethylpiperidine

Product 1

HCID 193917364-Benzoyloxy-1-ethoxy-2,2,6,6-tetramethylpiperidineYield 48.5%

Reagents, catalysts & solvents 4

HCID 23938PalladiumCatalystHCID 679Dimethyl SulfoxideSolventHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

A mixture of 28.3 grams (102 mmol) of 4-benzoyloxy-1-oxyl-2,2,6,6-tetramethylpiperidine, 5.0 grams of magnesium sulfate, 1.0 gram of 5% palladium on carbon, and 100 ml of anhydrous tetrahydrofuran is hydrogenated (50 psi, room temperature) in a Parr apparatus. Solids are removed by filtration, and ethyl iodide (32.1 grams, 206 mmol) is added to the crude hydroxylamine solution. A solution obtained by refluxing a suspension of 3.7 grams (154 mmol) of sodium hydride in 50 ml of dimethyl sulfoxide and 50 ml of tetrahydrofuran is then added over 30 minutes to the hydroxylamine solution. The reaction mixture is diluted with water (1000 ml) and extracted with ether (2×150 ml). The combined organic layers are washed with water (2×1000 ml), washed with saturated sodium chloride solution (500 ml), dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The crude product is purified by flash chromatography (silica gel; 9:1 hexane:ethyl acetate) and crystallized from methanol to afford 15.1 grams (48% yield) of the title compound as a white solid melting at 76-78° C.

Workup

  1. custom(50 psi, room temperature)
  2. customA solution obtained
  3. temperatureby refluxing
  4. extractionextracted with ether (2×150 ml)
  5. washThe combined organic layers are washed with water (2×1000 ml)
  6. washwashed with saturated sodium chloride solution (500 ml)
  7. dry with materialdried over anhydrous magnesium sulfate
  8. concentrationconcentrated under reduced pressure
  9. customThe crude product is purified by flash chromatography (silica gel; 9:1 hexane:ethyl acetate)
  10. customcrystallized from methanol

Sources & evidence

ORD record
ord-f1f1c6ed903943ba88ac29cc1965253e
Source dataset
uspto-grants-1991_06
Patent number
US05021481

Reaction notes

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