Sodium Hydroxide → 3,6-Dichloro-4-[methyl(oxan-4-yl)amino]pyridine-2-carboxylic acid

HRID 2208801Notes

Reaction equation

HRID 2208801 reaction equation
[Cl:1][C:2]1[C:3]([C:17]([O:19]C)=[O:18])=[N:4][C:5]([Cl:16])=[CH:6][C:7]=1[N:8]([CH3:15])[CH:9]1[CH2:14][CH2:13][O:12][CH2:11][CH2:10]1.[OH-].[Na+]>C1COCC1>[Cl:1][C:2]1[C:3]([C:17]([OH:19])=[O:18])=[N:4][C:5]([Cl:16])=[CH:6][C:7]=1[N:8]([CH3:15])[CH:9]1[CH2:10][CH2:11][O:12][CH2:13][CH2:14]1

Participants

4

Reactant 2

HCID 14798Sodium HydroxideHCID 86719558Methyl 3,6-dichloro-4-[methyl(oxan-4-yl)amino]pyridine-2-carboxylate

Product 1

HCID 867195593,6-Dichloro-4-[methyl(oxan-4-yl)amino]pyridine-2-carboxylic acidYield 78%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a stirred solution of methyl 3,6-dichloro-4-[methyl(oxan-4-yl)amino]pyridine-2-carboxylate (114 mg, 0.36 mmol) in THF (5 ml) was added 2M aqueous NaOH (0.89 ml, 1.79 mmol) and the reaction mixture was left to stir at room temperature for 20 h after which time the THF was evaporated in vacuo. The aqueous phase was then treated with an aqueous 10% citric acid solution to pH 5-6 and then extracted with EtOAc (3×50 ml) followed by a solution of 1:1 IPA/CHCl3 (2×50 ml), the combined organic phases were then washed with brine (50 ml) dried with Na2SO4 and evaporated to give the title compound as a white solid (85 mg, 78%). LC-MS 100%, 1.47 min (3.5 minute LC-MS method), m/z=305.5/306.9, 1H NMR (500 MHz, Methanol-d4) δ 7.10 (s, 1H), 4.03 (dd, J=11.5, 4.4 Hz, 2H), 3.99-3.86 (m, 1H), 3.47 (t, J=11.0 Hz, 2H), 2.90 (s, 3H), 2.05-1.90 (m, 2H), 1.74 (d, J=12.4 Hz, 2H).

Workup

  1. waitthe reaction mixture was left
  2. customwas evaporated in vacuo
  3. additionThe aqueous phase was then treated with an aqueous 10% citric acid solution to pH 5-6
  4. extractionextracted with EtOAc (3×50 ml)
  5. washthe combined organic phases were then washed with brine (50 ml)
  6. dry with materialdried with Na2SO4
  7. customevaporated

Sources & evidence

ORD record
ord-52f11550359a44bfa5589030accd47d8
Source dataset
uspto-grants-2016_06
Patent number
US09376422B2

Reaction notes

Loading…