Lithium hydroxide, monohydrate → 5-(3,3-Difluoroazetidin-1-yl)-6-(2-fluoroethoxyl)pyridine-2-carboxylic acid

HRID 625021Notes

Reaction equation

HRID 625021 reaction equation
[F:1][C:2]1([F:20])[CH2:5][N:4]([C:6]2[CH:7]=[CH:8][C:9]([C:16]([O:18]C)=[O:17])=[N:10][C:11]=2[O:12][CH2:13][CH2:14][F:15])[CH2:3]1.O.[OH-].[Li+]>O1CCCC1.O>[F:20][C:2]1([F:1])[CH2:5][N:4]([C:6]2[CH:7]=[CH:8][C:9]([C:16]([OH:18])=[O:17])=[N:10][C:11]=2[O:12][CH2:13][CH2:14][F:15])[CH2:3]1

Participants

5

Reactant 2

HCID 168937Lithium hydroxide, monohydrateHCID 90203373Methyl 5-(3,3-difluoroazetidin-1-yl)-6-(2-fluoroethoxyl)pyridine-2-carboxylate

Product 1

HCID 902039205-(3,3-Difluoroazetidin-1-yl)-6-(2-fluoroethoxyl)pyridine-2-carboxylic acid

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

A solution of methyl 5-(3,3-difluoroazetidin-1-yl)-6-(2-fluoroethoxyl)pyridine-2-carboxylate (Example 147 b, 73 mg, 252 μmol) and lithium hydroxide hydrate (12.7 mg, 302 μmol) in tetrahydrofuran (500 μL) and water (50.0 μL) was stirred for 12 h at ambient temperature. The reaction mixture was poured onto ice/0.1 N HCl (25 mL) and extracted with EtOAc (2×25 mL). The combined extracts were washed with ice/brine (25 mL), dried over Na2SO4, filtered and evaporated to dryness to give the target compound (69 mg, quant.) as off-white solid, MS (ESI) m/e=277.1 [MH+].

Workup

  1. additionThe reaction mixture was poured onto ice/0.1 N HCl (25 mL)
  2. extractionextracted with EtOAc (2×25 mL)
  3. washThe combined extracts were washed with ice/brine (25 mL)
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. customevaporated to dryness
  7. customto give the target compound (69 mg, quant.) as off-white solid, MS (ESI) m/e=277.1 [MH+]

Sources & evidence

ORD record
ord-f673212eb5994849821b2d40f812eb4f
Source dataset
uspto-grants-2016_04
Patent number
US09303012B2

Reaction notes

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