Water → 5-((R)-alpha-methylbenzyl)-7-hydroxy-5-azaspiro[2.4]heptane

HRID 1975338Notes

Reaction equation

HRID 1975338 reaction equation
O=[C:2]1[N:8]([C@@H:9]([C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)[CH3:10])[CH2:7][C:6](=[O:17])[C:3]21[CH2:5][CH2:4]2.[H-].[Al+3].[Li+].[H-].[H-].[H-].O.[OH-].[Na+]>O1CCCC1>[OH:17][CH:6]1[C:3]2([CH2:5][CH2:4]2)[CH2:2][N:8]([C@@H:9]([C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)[CH3:10])[CH2:7]1

Participants

6

Reactant 4

HCID 962Water2×HCID 14798Sodium HydroxideHCID 11775986HCID 11775986, compoundHCID 21226445Aluminium lithium hydride

Product 1

HCID 228504715-((R)-alpha-methylbenzyl)-7-hydroxy-5-azaspiro[2.4]heptaneYield 98.5%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

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 refluxed for 16 hours
  2. customThe insoluble material was removed by filtration
  3. concentrationthe filtrate was concentrated to dryness

Sources & evidence

ORD record
ord-dc0771712caa459c83d3758fe150b993
Source dataset
uspto-grants-1994_02
Patent number
US05286723

Reaction notes

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