Ethyl isobutyrate → 1-phenylmethyl-alpha,alpha-dimethyl-4-hydroxy-4-piperidine-acetic Acid Ethyl Ester

HRID 977160Notes

Reaction equation

HRID 977160 reaction equation
C([Li])CCC.CC(NC(C)C)C.[CH2:13]([O:15][C:16](=[O:20])[CH:17]([CH3:19])[CH3:18])[CH3:14].[C:21]1([CH2:27][N:28]2[CH2:33][CH2:32][C:31](=[O:34])[CH2:30][CH2:29]2)[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1>O1CCCC1>[CH2:13]([O:15][C:16](=[O:20])[C:17]([CH3:19])([CH3:18])[C:31]1([OH:34])[CH2:32][CH2:33][N:28]([CH2:27][C:21]2[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=2)[CH2:29][CH2:30]1)[CH3:14]

Participants

6

Reactant 4

HCID 7342Ethyl isobutyrateHCID 7912DiisopropylamineHCID 192201-Benzyl-4-piperidoneHCID 178418339Butyllithium

Product 1

HCID 542124921-phenylmethyl-alpha,alpha-dimethyl-4-hydroxy-4-piperidine-acetic Acid Ethyl EsterYield 76%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
-70 °C

Procedure

125 ml of 1.6M butyllithium was added dropwise to a solution of 18.5 g (0.18 mole) of N-(1-methylethyl)-2-propanamine in 75 ml of tetrahydrofuran, cooled to a temperature of -70° C. The mixture was stirred for ten minutes at this temperature then 17.5 g ( 0.15 mole ) of 2-methyl-propanoic acid ethyl ester in solution in 70 ml of tetrahydrofuran was added, keeping the temperature at -70° C. After stirring for one hour at this temperature, a solution of 26 g (0.14 mole) of 1-phenylmethyl-4-piperidinone in 70 ml of tetrahydrofuran was added. The reaction medium was stirred for 1.5 h at a temperature of -70° C. and was then allowed to return to room temperature. After evaporating off the solvents under reduced pressure, the residue was poured into a saturated solution of ammonium chloride. The organic phase was extracted with ether, washed with water, dried over magnesium sulphate and filtered and the solvents were evaporated off under reduced pressure. After purification by distillation, 32 g (yield: 76%) of the desired product was obtained as an oil. B Pt=145°-150° C. (0.05 mm Hg, i.e. about 6.66 Pa)

Workup

  1. customat -70° C
  2. stirringAfter stirring for one hour at this temperature
  3. stirringThe reaction medium was stirred for 1.5 h at a temperature of -70° C.
  4. customto return to room temperature
  5. customAfter evaporating off the solvents under reduced pressure
  6. additionthe residue was poured into a saturated solution of ammonium chloride
  7. extractionThe organic phase was extracted with ether
  8. washwashed with water
  9. dry with materialdried over magnesium sulphate
  10. filtrationfiltered
  11. customthe solvents were evaporated off under reduced pressure
  12. customAfter purification
  13. distillationby distillation

Sources & evidence

ORD record
ord-7c77f61d21854077887f740e7b322152
Source dataset
uspto-grants-1997_03
Patent number
US05614534

Reaction notes

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