Methyl 2-(5-fluoro-2-(methyloxy)-4-pyridinyl)-5-(hydroxymethyl)benzoate → 1-(2-(5-Fluoro-2-(methyloxy)-4-pyridinyl)-5-(hydroxymethyl)phenyl)-2,2-dimethyl-1-propanone

HRID 404333Notes

Reaction equation

HRID 404333 reaction equation
[F:1][C:2]1[C:3]([C:10]2[CH:19]=[CH:18][C:17]([CH2:20][OH:21])=[CH:16][C:11]=2[C:12]([O:14]C)=O)=[CH:4][C:5]([O:8][CH3:9])=[N:6][CH:7]=1.[C:22]([Li])([CH3:25])([CH3:24])[CH3:23]>C1COCC1>[F:1][C:2]1[C:3]([C:10]2[CH:19]=[CH:18][C:17]([CH2:20][OH:21])=[CH:16][C:11]=2[C:12](=[O:14])[C:22]([CH3:25])([CH3:24])[CH3:23])=[CH:4][C:5]([O:8][CH3:9])=[N:6][CH:7]=1

Participants

4

Reactant 2

HCID 57467597Methyl 2-(5-fluoro-2-(methyloxy)-4-pyridinyl)-5-(hydroxymethyl)benzoateHCID 178418306HCID 178418306, compound

Product 1

HCID 577061591-(2-(5-Fluoro-2-(methyloxy)-4-pyridinyl)-5-(hydroxymethyl)phenyl)-2,2-dimethyl-1-propanoneYield 88.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a stirred solution of methyl 2-(5-fluoro-2-methoxypyridin-4-yl)-5-(hydroxymethyl)benzoate T6.3 (0.307 g, 1 mmol) in THF (11 mL) at −78° C. was added tert-butyl lithium (2 mL, 3 mmol). The resulting mixture was stirred for one hour. The reaction was then quenched with a saturated solution of ammonium chloride and extracted three times with EtOAc. The combined organic layers were dried over anhydrous magnesium sulfate, filtered, and the organic solvent was removed under reduced pressure. The residue was then purified on silica gel (0-40% EtOAc in hexanes) to yield T6.4 as a colorless solid (0.28 g, 84% yield).

Workup

  1. customThe reaction was then quenched with a saturated solution of ammonium chloride
  2. extractionextracted three times with EtOAc
  3. dry with materialThe combined organic layers were dried over anhydrous magnesium sulfate
  4. filtrationfiltered
  5. customthe organic solvent was removed under reduced pressure
  6. customThe residue was then purified on silica gel (0-40% EtOAc in hexanes)

Sources & evidence

ORD record
ord-04a3b4c895324c66bd092903439e2d1d
Source dataset
uspto-grants-2014_06
Patent number
US08748462B2

Reaction notes

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