Lithium hydroxide, monohydrate → (R)-Quinuclidin-3-yl((3-(3-hydroxypropoxy)phenyl)(phenyl)methyl)carbamate

HRID 332707Notes

Reaction equation

HRID 332707 reaction equation
C([O:9][CH2:10][CH2:11][CH2:12][O:13][C:14]1[CH:19]=[CH:18][CH:17]=[C:16]([CH:20]([C:33]2[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=2)[NH:21][C:22]([O:24][C@@H:25]2[CH:30]3[CH2:31][CH2:32][N:27]([CH2:28][CH2:29]3)[CH2:26]2)=[O:23])[CH:15]=1)(=O)C1C=CC=CC=1.O.[OH-].[Li+]>CO.O>[N:27]12[CH2:28][CH2:29][CH:30]([CH2:31][CH2:32]1)[C@@H:25]([O:24][C:22](=[O:23])[NH:21][CH:20]([C:16]1[CH:17]=[CH:18][CH:19]=[C:14]([O:13][CH2:12][CH2:11][CH2:10][OH:9])[CH:15]=1)[C:33]1[CH:34]=[CH:35][CH:36]=[CH:37][CH:38]=1)[CH2:26]2

Participants

5

Reactant 2

HCID 168937Lithium hydroxide, monohydrate2×HCID 710930683-(3-(phenyl((((R)-quinuclidin-3-yloxy)carbonyl)amino)-methyl)phenoxy)propyl benzoate

Product 1

HCID 117680437(R)-Quinuclidin-3-yl((3-(3-hydroxypropoxy)phenyl)(phenyl)methyl)carbamateYield 93%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 962WaterSolvent

Procedure

To a stirred solution of 3-(3-(phenyl((((R)-quinuclidin-3-yloxy)carbonyl)amino)-methyl)phenoxy)propyl benzoate (0.370 g, 0.72 mmol) in methanol (3.6 mL), was added a solution of lithium hydroxide monohydrate (0.060 g, 1.44 mmol) in water (1.2 mL). The reaction mixture was stirred at room temperature for 1 hour. Further lithium hydroxide monohydrate (0.060 g, 1.44 mmol) was added, and the reaction stirred at room temperature for a further 16 hours. The reaction mixture was heated at 40° C. for 3.5 hours and allowed to cool. The solvent was evaporate at reduced pressure, and the residue partitioned between ethyl acetate and water. The aqueous phase was further extracted with ethyl acetate (×2). The combined organic extracts were washed with 10% aqueous potassium carbonate (×2), saturated brine, and dried with anhydrous sodium sulfate. The mixture was filtered and the solvent evaporated at reduced pressure to afford the title compound (0.275 g, 93%).

Workup

  1. stirringthe reaction stirred at room temperature for a further 16 hours
  2. temperatureThe reaction mixture was heated at 40° C. for 3.5 hours
  3. temperatureto cool
  4. customThe solvent was evaporate at reduced pressure
  5. customthe residue partitioned between ethyl acetate and water
  6. extractionThe aqueous phase was further extracted with ethyl acetate (×2)
  7. washThe combined organic extracts were washed with 10% aqueous potassium carbonate (×2), saturated brine
  8. dry with materialdried with anhydrous sodium sulfate
  9. filtrationThe mixture was filtered
  10. customthe solvent evaporated at reduced pressure

Sources & evidence

ORD record
ord-ef77d7bb14e74f828fcc2cf5570dba00
Source dataset
uspto-grants-2014_11
Patent number
US08877774B2

Reaction notes

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