tert-butyl {(S)-1-benzyloxymethyl-2-[2-oxo-2-(3,4,5-trifluorophenyl)ethoxy]ethyl}carbamate → [(3S,5R)-5-(3,4,5-trifluorophenyl)morpholin-3-yl]methanol

HRID 1677055Notes

Reaction equation

HRID 1677055 reaction equation
C(OC(=O)[NH:7][C@@H:8]([CH2:23][O:24]CC1C=CC=CC=1)[CH2:9][O:10][CH2:11][C:12](=O)[C:13]1[CH:18]=[C:17]([F:19])[C:16]([F:20])=[C:15]([F:21])[CH:14]=1)(C)(C)C>Cl.C(OCC)(=O)C>[F:21][C:15]1[CH:14]=[C:13]([C@H:12]2[NH:7][C@@H:8]([CH2:23][OH:24])[CH2:9][O:10][CH2:11]2)[CH:18]=[C:17]([F:19])[C:16]=1[F:20]

Participants

3

Reactant 1

HCID 67373700tert-butyl {(S)-1-benzyloxymethyl-2-[2-oxo-2-(3,4,5-trifluorophenyl)ethoxy]ethyl}carbamate

Product 1

HCID 67373759[(3S,5R)-5-(3,4,5-trifluorophenyl)morpholin-3-yl]methanolYield 49.6%

Reagents, catalysts & solvents 1

HCID 21866389Hydrogen chloride-ethyl acetateSolvent

Procedure

{(S)-1-benzyloxymethyl-2-[2-oxo-2-(3,4,5-trifluorophenyl)ethoxy]ethyl}carbamic acid t-butyl ester (82.6 g) was diluted with 4 N hydrochloric acid-ethyl acetate solution (500 mL), and the resultant was stirred at room temperature for 12 hours. The solvent was removed under a vacuum, and the resultant was dissolved in methanol (500 mL). 10% palladium on carbon (8.5 g, 50% water content) was added, and under a hydrogen atmosphere, stirring was continued for 22 hours. The catalyst was filtered off on celite, and the filtrate was concentrated under a vacuum. The residue was diluted with methanol (500 mL), and 20% palladium hydroxide on carbon (8 g, 50% water content) was added, and under a hydrogen atmosphere, stirring was continued for 4 hours. The catalyst was filtered off on celite, and the solvent was removed under a vacuum. Ethyl acetate (600 mL) and 1 N sodium hydroxide solution (250 mL) was added, and the organic layer was partitioned. The organic layer was washed with brine and dried over anhydrous magnesium sulfate. The residue was suspended in ether (80 mL) and the resultant was filtered, and the title compound (22.34 g) was obtained. The physical property values are as follows.

Workup

  1. customThe solvent was removed under a vacuum
  2. dissolutionthe resultant was dissolved in methanol (500 mL)
  3. addition10% palladium on carbon (8.5 g, 50% water content) was added
  4. stirringunder a hydrogen atmosphere, stirring
  5. waitwas continued for 22 hours
  6. filtrationThe catalyst was filtered off on celite
  7. concentrationthe filtrate was concentrated under a vacuum
  8. additionThe residue was diluted with methanol (500 mL), and 20% palladium hydroxide on carbon (8 g, 50% water content)
  9. additionwas added
  10. stirringunder a hydrogen atmosphere, stirring
  11. waitwas continued for 4 hours
  12. filtrationThe catalyst was filtered off on celite
  13. customthe solvent was removed under a vacuum
  14. additionEthyl acetate (600 mL) and 1 N sodium hydroxide solution (250 mL) was added
  15. customthe organic layer was partitioned
  16. washThe organic layer was washed with brine
  17. dry with materialdried over anhydrous magnesium sulfate
  18. filtrationthe resultant was filtered

Sources & evidence

ORD record
ord-3ee4d3a5d5d54b12b21c12530f89c10a
Source dataset
uspto-grants-2011_08
Patent number
US08008293B2

Reaction notes

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