Lithium Hydroxide → 5-(Difluoromethoxy)picolinic acid

HRID 1911028Notes

Reaction equation

HRID 1911028 reaction equation
[F:1][CH:2]([F:14])[O:3][C:4]1[CH:5]=[CH:6][C:7]([C:10]([O:12]C)=[O:11])=[N:8][CH:9]=1.[OH-].[Li+]>C1COCC1.O>[F:14][CH:2]([F:1])[O:3][C:4]1[CH:5]=[CH:6][C:7]([C:10]([OH:12])=[O:11])=[N:8][CH:9]=1

Participants

5

Reactant 2

HCID 3939Lithium HydroxideHCID 57827732Methyl 5-(difluoromethoxy)picolinate

Product 1

HCID 574758715-(Difluoromethoxy)picolinic acidYield 90%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of methyl 5-(difluoromethoxy)picolinate from step K2 (730 mg, 3.59 mmol) in THF (8 mL), was added a solution of lithium hydroxide (430 mg, 18.0 mmol) in water (5 mL). The mixture was stirred at rt for 3 h, then concentrated in vacuo. After the addition of 10 mL of 1 N HCl, 150 mL of EtOAc was added. The resulting mixture was washed with water. The organic layer was dried over sodium sulfate, filtered, and concentrated in vacuo to afford 5-(difluoromethoxy)picolinic acid (610 mg, 3.23 mmol, 90% yield). LCMS (M+H)+=190.1. 1H NMR (500 HMz, chloroform-d) δ 8.52 (d, J=2.0 Hz, 1H), 8.30 (d, J=8.5 Hz, 1H), 7.74 (dd, J=8.5, 2.6 Hz, 1H), 6.84-6.53 (m, 1H).

Workup

  1. concentrationconcentrated in vacuo
  2. additionAfter the addition of 10 mL of 1 N HCl, 150 mL of EtOAc
  3. additionwas added
  4. washThe resulting mixture was washed with water
  5. dry with materialThe organic layer was dried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-1abfaf2e930a4562900aec238a1e2bdd
Source dataset
uspto-grants-2013_12
Patent number
US08604024B2

Reaction notes

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