Sodium Hydroxide → 4-({1-[(Tert-butoxy)carbonyl]piperidin-4-yl}(methyl)amino)-3,6-dichloropyridine-2-carboxylic acid

HRID 2208797Notes

Reaction equation

HRID 2208797 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([N:14]([CH3:27])[C:15]2[CH:20]=[C:19]([Cl:21])[N:18]=[C:17]([C:22]([O:24]C)=[O:23])[C:16]=2[Cl:26])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[OH-].[Na+]>C1COCC1>[C:1]([O:5][C:6]([N:8]1[CH2:9][CH2:10][CH:11]([N:14]([CH3:27])[C:15]2[CH:20]=[C:19]([Cl:21])[N:18]=[C:17]([C:22]([OH:24])=[O:23])[C:16]=2[Cl:26])[CH2:12][CH2:13]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

4

Reactant 2

HCID 14798Sodium HydroxideHCID 86719553Methyl 4-({1-[(tert-butoxy)carbonyl]piperidin-4-yl}(methyl)amino)-3,6-dichloropyridine-2-carboxylate

Product 1

HCID 867195544-({1-[(Tert-butoxy)carbonyl]piperidin-4-yl}(methyl)amino)-3,6-dichloropyridine-2-carboxylic acidYield 84%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a stirred solution of methyl 4-({1-[(tert-butoxy)carbonyl]piperidin-4-yl}(methyl)amino)-3,6-dichloropyridine-2-carboxylate (95 mg, 0.23 mmol) in THF (5 ml) was added 2M aqueous NaOH (2.3 ml, 4.54 mmol) and the reaction mixture was left to stir at room temperature for 16 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), the combined organic phases were then dried with Na2SO4 and evaporated to give the title compound as a white powder (77 mg, 84%). LC-MS 100%, 2.02 min (3.5 minute LC-MS method), m/z=403.9/405.6, 1H NMR (500 MHz, Methanol-d4) δ 7.09 (s, 1H) 4.14-4.22 (m, 2H) 3.80-3.89 (m, 1H) 2.84 (s, 5H) 1.74-1.81 (m, 4H) 1.46 (s, 9H).

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. dry with materialthe combined organic phases were then dried with Na2SO4
  6. customevaporated

Sources & evidence

ORD record
ord-383b711c77de4a34a4ec9009645ca32d
Source dataset
uspto-grants-2016_06
Patent number
US09376422B2

Reaction notes

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