Sodium Hydroxide → 4-Amino-4-[1-(4-chlorophenyl)cyclobutyl]-2-methylbutan-2-ol

HRID 728274Notes

Reaction equation

HRID 728274 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2([C:12](=[N:18]O)[CH2:13][C:14]([OH:17])([CH3:16])[CH3:15])[CH2:11][CH2:10][CH2:9]2)=[CH:4][CH:3]=1.[H-].[Al+3].[Li+].[H-].[H-].[H-].C(O)(=O)/C=C\C(O)=O.[OH-].[Na+]>O1CCCC1.CCOCC.O>[NH2:18][CH:12]([C:8]1([C:5]2[CH:6]=[CH:7][C:2]([Cl:1])=[CH:3][CH:4]=2)[CH2:9][CH2:10][CH2:11]1)[CH2:13][C:14]([CH3:16])([OH:17])[CH3:15]

Participants

8

Reactant 4

HCID 14798Sodium HydroxideHCID 444266Maleic AcidHCID 21226445Aluminium lithium hydrideHCID 867439361-[1-(4-Chlorophenyl)cyclobutyl]-3-hydroxy-3-methylbutan-1-one oxime

Product 1

HCID 99215244-Amino-4-[1-(4-chlorophenyl)cyclobutyl]-2-methylbutan-2-ol

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 3283Diethyl EtherSolvent2×HCID 8028TetrahydrofuranSolvent

Procedure

A solution of 1-[1-(4-chlorophenyl)cyclobutyl]-3-hydroxy-3-methylbutan-1-one oxime (3 g prepared as described in Example 84 above) in dry tetrahydrofuran (20 ml) was added under nitrogen to lithium aluminium hydride (2 g). The mixture was heated under reflux for 3 hours and then left without further heating for 16 hours. Water (100 ml) was added dropwise and the organic layer was separated. The aqueous layer was extracted with ether and the extracts combined with the organic layer and dried. The solvents were evaporated to give an oil which was dissolved in ether. Addition of a solution of maleic acid in ether gave a gum which slowly solidified. The solid was added to an aqueous solution of sodium hydroxide and the mixture extracted with ether. Removal of the ether gave an oil which was purified by high performance liquid chromatography to give 4-amino-4-[1-(4-chlorophenyl)cyclobutyl]-2-methylbutan-2-ol (m.p. 60°-62° C. shrinks 50° C.).

Workup

  1. temperatureThe mixture was heated
  2. temperatureunder reflux for 3 hours
  3. waitleft
  4. temperaturewithout further heating for 16 hours
  5. customthe organic layer was separated
  6. extractionThe aqueous layer was extracted with ether
  7. customdried
  8. customThe solvents were evaporated
  9. customto give an oil which
  10. customgave a gum which
  11. extractionthe mixture extracted with ether
  12. customRemoval of the ether
  13. customgave an oil which
  14. customwas purified by high performance liquid chromatography

Sources & evidence

ORD record
ord-3dfcded19f154614aeb6ef04be29d4b6
Source dataset
uspto-grants-1991_09
Patent number
US05047432

Reaction notes

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