1-Methyl-1,4-cyclohexadiene → (R)-5-(2-Amino-1-hydroxyethyl)-8-hydroxyquinolin-2(1H)-one hydrochloride

HRID 874803Notes

Reaction equation

HRID 874803 reaction equation
[N:1]([CH2:4][C@@H:5]([C:14]1[CH:23]=[CH:22][C:21]([O:24]CC2C=CC=CC=2)=[C:20]2[C:15]=1[CH:16]=[CH:17][C:18](=[O:32])[NH:19]2)[O:6][Si](C(C)(C)C)(C)C)=[N+]=[N-].CC1CC=CCC=1.[ClH:40].O1CCOCC1>C(O)C.[Pd]>[ClH:40].[NH2:1][CH2:4][C@@H:5]([C:14]1[CH:23]=[CH:22][C:21]([OH:24])=[C:20]2[C:15]=1[CH:16]=[CH:17][C:18](=[O:32])[NH:19]2)[OH:6]

Participants

6

Reactant 3

HCID 780061-Methyl-1,4-cyclohexadieneHCID 204431481,4-Dioxane hydrochlorideHCID 58505233(R)-5-(2-Azido-1-((tert-butyldimethylsilyl)oxy)ethyl)-8-(benzyloxy)quinolin-2(1H)-one

Product 1

HCID 71093241(R)-5-(2-Amino-1-hydroxyethyl)-8-hydroxyquinolin-2(1H)-one hydrochlorideYield 64.3%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 702EthanolSolvent

Conditions

Temperature
60 °C

Procedure

To a solution of (R)-5-(2-azido-1-((tert-butyldimethylsilyl)oxy)ethyl)-8-(benzyloxy)quinolin-2(1H)-one (4.50 g, 10.0 mmol) in ethanol (50 mL) was added 10% palladium on charcoal (4.50 g) followed by 1-methyl-1,4-cyclohexadiene (11.0 mL, 97.9 mmol). The reaction was warmed to 60° C. (CARE—POSSIBLE EXOTHERM) and then stirred at 60° C. for 2 hours. The reaction mixture was allowed to cool and filtered through a pad of celite. The filter cake was washed with further ethanol and the filtrate was evaporated at reduced pressure. The residue was evaporated from iso-propanol (×2) and dissolved in iso-propanol (30 mL). HCl-dioxane (4 M, 50 mL, 200 mmol) was added and the reaction mixture stirred at RT for 18 hours. The resultant suspension was filtered, the filter cake washed with ether and the solid dried under vacuum in the presence of P2O5 to afford the title compound (1.65 g, 62%).

Workup

  1. temperatureto cool
  2. filtrationfiltered through a pad of celite
  3. washThe filter cake was washed with further ethanol
  4. customthe filtrate was evaporated at reduced pressure
  5. customThe residue was evaporated from iso-propanol (×2)
  6. dissolutiondissolved in iso-propanol (30 mL)
  7. stirringthe reaction mixture stirred at RT for 18 hours
  8. filtrationThe resultant suspension was filtered
  9. washthe filter cake washed with ether
  10. dry with materialthe solid dried under vacuum in the presence of P2O5

Sources & evidence

ORD record
ord-fc23fa6bd2ca4bf895a5a9e6ed3c2fa5
Source dataset
uspto-grants-2015_03
Patent number
US08980913B2

Reaction notes

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