Hydrochloric Acid → [(R)-1-hydroxymethyl-3-(4-heptyloxy-phenyl)-1-methyl-propyl]-carbamic acid tert-butyl ester

HRID 12584

Reaction equation

HRID 12584 reaction equation
[C:1]([O:5][C:6](=[O:21])[NH:7][C@:8]([CH2:19][OH:20])([CH3:18])[CH2:9][CH2:10][C:11]1[CH:16]=[CH:15][C:14]([OH:17])=[CH:13][CH:12]=1)([CH3:4])([CH3:3])[CH3:2].C(=O)([O-])[O-].[K+].[K+].[CH2:28](OS(C)(=O)=O)[CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][CH3:34].Cl>C(O)C.CCOC(C)=O>[C:1]([O:5][C:6](=[O:21])[NH:7][C@:8]([CH2:19][OH:20])([CH3:18])[CH2:9][CH2:10][C:11]1[CH:16]=[CH:15][C:14]([O:17][CH2:28][CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][CH3:34])=[CH:13][CH:12]=1)([CH3:4])([CH3:2])[CH3:3]

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 11430Potassium CarbonateHCID 11528510Heptyl methanesulfonateHCID 59655583[(R)-1-hydroxymethyl-3-(4-hydroxy-phenyl)-1-methyl-propyl]-carbamic acid tert-butyl ester

Product 1

HCID 12964546[(R)-1-hydroxymethyl-3-(4-heptyloxy-phenyl)-1-methyl-propyl]-carbamic acid tert-butyl ester

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a stirred solution of [(R)-1-hydroxymethyl-3-(4-hydroxy-phenyl)-1-methyl-propyl]-carbamic acid tert-butyl ester (2.06 g, 6.98 mMol) in ethanol (100 ml) is added potassium carbonate (2.90 g, 20.8 mMol) and methanesulfonic acid heptyl ester (2.04 g, 10.5 mMol). The mixture is heated to reflux temperature and stirred at that temperature for 6 hours. The mixture is then cooled to RT and stirred at RT overnight. The reaction mixture is then poured onto a biphasic mixture of AcOEt and HCl (aqueous, 1 M). The aqueous phase is extracted twice with AcOEt. The combined organic layers are washed with NaHCO3 (saturated aqueous solution), dried (Na2SO4) and concentrated under reduced pressure. Column chromatography eluting with 8% AcOEt in toluene gives the title compound as a colourless oil.

Workup

  1. temperatureThe mixture is heated
  2. temperatureto reflux temperature
  3. stirringstirred at RT overnight
  4. extractionThe aqueous phase is extracted twice with AcOEt
  5. washThe combined organic layers are washed with NaHCO3 (saturated aqueous solution)
  6. dry with materialdried (Na2SO4)
  7. concentrationconcentrated under reduced pressure
  8. washColumn chromatography eluting with 8% AcOEt in toluene

Sources & evidence

ORD record
ord-70054e6b95a147cabccc72cb3935270a
Source dataset
uspto-grants-2010_06
Patent number
US07728020B2

Linked notes

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