Acetaldehyde → 2,3,4-trifluoro-6-(1-hydroxyethyl)-5-pivaloylamino-O-tetrahydropyranylphenol

HRID 1736250Notes

Reaction equation

HRID 1736250 reaction equation
[F:1][C:2]1[C:7]([F:8])=[C:6]([F:9])[C:5]([NH:10][C:11](=[O:16])[C:12]([CH3:15])([CH3:14])[CH3:13])=[CH:4][C:3]=1[O:17][CH:18]1[CH2:23][CH2:22][CH2:21][CH2:20][O:19]1.C([Li])CCC.[CH:29](=[O:31])[CH3:30].O>O1CCCC1.CCCCCC>[F:1][C:2]1[C:7]([F:8])=[C:6]([F:9])[C:5]([NH:10][C:11](=[O:16])[C:12]([CH3:15])([CH3:14])[CH3:13])=[C:4]([CH:29]([OH:31])[CH3:30])[C:3]=1[O:17][CH:18]1[CH2:23][CH2:22][CH2:21][CH2:20][O:19]1

Participants

7

Reactant 4

HCID 177AcetaldehydeHCID 962WaterHCID 867496582,3,4-trifluoro-5-pivaloylamino-O-tetrahydropyranylphenolHCID 178418339Butyllithium

Product 1

HCID 867496592,3,4-trifluoro-6-(1-hydroxyethyl)-5-pivaloylamino-O-tetrahydropyranylphenolYield 60%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8058HexaneSolvent

Conditions

Temperature
-35 °C

Procedure

3.60 g (10.9 mmol) of the above 2,3,4-trifluoro-5-pivaloylamino-O-tetrahydropyranylphenol was dissolved in 50 mL of tetrahydrofuran, 14 mL of a 1.6 M solution of n-butyl lithium in n-hexane was added dropwise to the solution at an internal temperature of -60° C. or below, the mixture was warmed to -35° C. and cooled again to -60° C. or below. About 2 mL of acetaldehyde was added thereto in a gaseous condition and the mixture was stirred for 20 minutes. Water was added to the reaction solution, the mixture was warmed to room temperature and extracted once with ethyl acetate. The organic layer was washed once with water and once with an aqueous saturated solution of sodium chloride and dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure and the residue was purified by silica gel column chromatography (n-hexane:ethyl acetate=5:1-3:1) to give 2.45 g of a mixture of diastereomers of 2,3,4-trifluoro-6-(1-hydroxyethyl)-5-pivaloylamino-O-tetrahydropyranylphenol (yield: 60%).

Workup

  1. temperaturecooled again to -60° C. or below
  2. temperaturethe mixture was warmed to room temperature
  3. extractionextracted once with ethyl acetate
  4. washThe organic layer was washed once with water and once with an aqueous saturated solution of sodium chloride
  5. dry with materialdried over anhydrous sodium sulfate
  6. distillationThe solvent was distilled off under reduced pressure
  7. customthe residue was purified by silica gel column chromatography (n-hexane:ethyl acetate=5:1-3:1)

Sources & evidence

ORD record
ord-fe9ddd7490bf4de2a60bb58e47a75f65
Source dataset
uspto-grants-1996_07
Patent number
US05539112

Reaction notes

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