Pyridine → 7-acetoxy-5-[1-(R)-phenylethyl]-5-azaspiro[2,4]heptane

HRID 1721103Notes

Reaction equation

HRID 1721103 reaction equation
[C:1]([O:4][C:5](=[O:7])[CH3:6])(=O)[CH3:2].N1C=CC=CC=1.OC1[C:19]2([CH2:21][CH2:20]2)[CH2:18][N:17]([C@@H:22]([C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)[CH3:23])C1>C(OCC)(=O)C>[C:5]([O:4][CH:1]1[C:19]2([CH2:20][CH2:21]2)[CH2:18][N:17]([C@@H:22]([C:24]2[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=2)[CH3:23])[CH2:2]1)(=[O:7])[CH3:6]

Participants

5

Reactant 3

HCID 1049PyridineHCID 7918Acetic AnhydrideHCID 228504715-((R)-alpha-methylbenzyl)-7-hydroxy-5-azaspiro[2.4]heptane

Product 1

HCID 228504707-acetoxy-5-[1-(R)-phenylethyl]-5-azaspiro[2,4]heptane

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

A suspension of 1.5 g of compound 12 and 500 mg of lithium aluminum hydride in 30 ml of tetrahydrofuran was refluxed for 16 hours. 0.5 ml of water, 0.5 ml of 15% aqueous sodium hydroxide and 1.5 ml of water were added to the mixture in the mentioned order, and the mixture was stirred at room temperature for 30 minutes. The insoluble material was removed by filtration and the filtrate was concentrated to dryness to yield 1.4 g of 7-hydroxy-5-[1-(R)-phenylethyl]-5-azaspiro[2.4]heptane as a pale yellow oil. 5 ml of acetic anhydride and 5 ml of pyridine were added to 1.4 g of 7-hydroxy-5-[1-(R)-phenylethyl]-5-azaspiro[2.4]heptane which was cooled on an ice-bath. The mixture was stirred at room temperature for 3 hours. Ethyl acetate was added thereto and the solution was washed with saturated aqueous sodium bicarbonate and water, then, dried over anhydrous sodium sulfate. The solvent was removed under reduced pressure to yield 1.6 g of 7-acetoxy-5-[1-(R)-phenylethyl]-5-azaspiro[2.4]heptane as a yellow oil. A mixture of 1.6 g of 7-acetoxy-5-[1-(R)-phenylethyl]-5-azaspiro[2.4]heptane and 1.2 g of palladium-on-carbon (50% water wet) in 20 ml of ethanol was shaken under 3.8 atm of pressured hydrogen atmosphere for 5 hours. During the reduction reaction, the reaction vessel was warmed by a tungsten lamp. The catalyst was removed by filtration and the solvent was removed under reduced pressure to give 880 mg of title compound 69 as an oil.

Workup

  1. temperaturewas cooled on an ice-bath
  2. washthe solution was washed with saturated aqueous sodium bicarbonate and water
  3. dry with materialdried over anhydrous sodium sulfate
  4. customThe solvent was removed under reduced pressure

Sources & evidence

ORD record
ord-3d8420bf599a4da5badda10e4ca196eb
Source dataset
uspto-grants-1996_04
Patent number
US05508428

Reaction notes

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