Hydrochloric Acid → [(3S,5R)-5-(3,4,5-trifluorophenyl)morpholin-3-yl]methanol

HRID 553957Notes

Reaction equation

HRID 553957 reaction equation
Cl.C([O:9][CH2:10][C@H:11]([NH:26]C(=O)OC(C)(C)C)[CH2:12][O:13][CH2:14][C:15](=O)[C:16]1[CH:21]=[C:20]([F:22])[C:19]([F:23])=[C:18]([F:24])[CH:17]=1)C1C=CC=CC=1>C(OCC)(=O)C>[F:24][C:18]1[CH:17]=[C:16]([C@H:15]2[NH:26][C@@H:11]([CH2:10][OH:9])[CH2:12][O:13][CH2:14]2)[CH:21]=[C:20]([F:22])[C:19]=1[F:23]

Participants

4

Reactant 2

HCID 313Hydrochloric AcidHCID 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 78.5%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent2×

Procedure

A solution of 4 N hydrochloric acid in ethyl acetate (30 mL) was added to a solution of tert-butyl {(S)-1-benzyloxymethyl-2-[2-oxo-2-(3,4,5-trifluorophenyl)ethoxy]ethyl}carbamate (3.55 g) in ethyl acetate (30 mL) at room temperature. The reaction solution was stirred at room temperature for one hour and then concentrated under reduced pressure. 10% palladium-carbon (containing 50% water, 167 mg) was added to a solution of the resulting residue in methanol (50 mL), and the reaction solution was stirred in a hydrogen atmosphere at room temperature for 18 hours. Palladium-carbon in the reaction solution was removed by filtration, and then the filtrate was concentrated under reduced pressure. A saturated sodium bicarbonate solution and ethyl acetate were added to the resulting residue, and the organic layer was separated. The organic layer was washed with brine. The resulting organic layer was dried over anhydrous magnesium sulfate and then concentrated under reduced pressure. The residue was purified by silica gel column chromatography (elution solvent: heptane-ethyl acetate system) to obtain 1.52 g of the title compound. The property values of the compound are as follows.

Workup

  1. concentrationconcentrated under reduced pressure
  2. addition10% palladium-carbon (containing 50% water, 167 mg) was added to a solution of the resulting residue in methanol (50 mL)
  3. stirringthe reaction solution was stirred in a hydrogen atmosphere at room temperature for 18 hours
  4. customPalladium-carbon in the reaction solution was removed by filtration
  5. concentrationthe filtrate was concentrated under reduced pressure
  6. additionA saturated sodium bicarbonate solution and ethyl acetate were added to the resulting residue
  7. customthe organic layer was separated
  8. washThe organic layer was washed with brine
  9. dry with materialThe resulting organic layer was dried over anhydrous magnesium sulfate
  10. concentrationconcentrated under reduced pressure
  11. customThe residue was purified by silica gel column chromatography (elution solvent: heptane-ethyl acetate system)

Sources & evidence

ORD record
ord-6fa2826ce7c5463b943432b8891bd6b8
Source dataset
uspto-grants-2011_11
Patent number
US08048878B2

Reaction notes

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