Hydrochloric Acid → 4-{[(2S)-2-fluoropropyl]oxy}pyridine

HRID 69123

Reaction equation

HRID 69123 reaction equation
[OH:1][C:2]1[CH:7]=[CH:6][N:5]=[CH:4][CH:3]=1.C(C=P(CCCC)(CCCC)CCCC)#N.[F:24][C@@H:25]([CH3:28])[CH2:26]O.Cl>C1(C)C=CC=CC=1.C(OCC)(=O)C>[F:24][C@@H:25]([CH3:28])[CH2:26][O:1][C:2]1[CH:7]=[CH:6][N:5]=[CH:4][CH:3]=1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 4622928CyanomethylenetributylphosphoraneHCID 11528331(2S)-2-fluoropropan-1-olHCID 178418642HCID 178418642, compound

Product 1

HCID 666961134-{[(2S)-2-fluoropropyl]oxy}pyridineYield 89.9%

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Procedure

A solution of 1.5 g of 4-hydroxypyridine, 7.6 g of cyanomethylenetributylphosphorane, and 1.4 g of (2S)-2-fluoro-1-propanol in 20 mL of toluene was stirred at 105° C. overnight. To the reaction mixture were added 1 M hydrochloric acid and ethyl acetate, and the organic layer was separated. The aqueous layer was adjusted to pH 11 by the addition of a 1 M aqueous sodium hydroxide solution, and extracted with ethyl acetate. The organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (chloroform/methanol) to obtain 2.2 g of 4-{[(2S)-2-fluoropropyl]oxy}pyridine.

Workup

  1. customthe organic layer was separated
  2. additionThe aqueous layer was adjusted to pH 11 by the addition of a 1 M aqueous sodium hydroxide solution
  3. extractionextracted with ethyl acetate
  4. washThe organic layer was washed with saturated brine
  5. dry with materialdried over anhydrous magnesium sulfate
  6. customthe solvent was evaporated under reduced pressure
  7. customThe residue was purified by silica gel column chromatography (chloroform/methanol)

Sources & evidence

ORD record
ord-7a62bb2315da4ddd9ab4f2c528883a6b
Source dataset
uspto-grants-2014_09
Patent number
US08822448B2

Linked notes

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