Sodium Hydroxide → Ethyl 5-cyano-6-methoxy-4-methylpicolinate

HRID 42492

Reaction equation

HRID 42492 reaction equation
[C:1]([C:3]1[C:8](=[O:9])[NH:7][C:6]([C:10]([O:12][CH2:13][CH3:14])=[O:11])=[CH:5][C:4]=1[CH3:15])#[N:2].F[B-](F)(F)F.[CH3:21][O+](C)C.[OH-].[Na+]>C(Cl)Cl>[C:1]([C:3]1[C:4]([CH3:15])=[CH:5][C:6]([C:10]([O:12][CH2:13][CH3:14])=[O:11])=[N:7][C:8]=1[O:9][CH3:21])#[N:2]

Participants

5

Reactant 3

HCID 14798Sodium HydroxideHCID 275523Ethyl 5-cyano-4-methyl-6-oxo-1,6-dihydropyridine-2-carboxylateHCID 2735153Oxonium, trimethyl-, tetrafluoroborate(1-) (1:1)

Product 1

HCID 67466404Ethyl 5-cyano-6-methoxy-4-methylpicolinateYield 52.9%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a stirred suspension of ethyl 5-cyano-4-methyl-6-oxo-1,6-dihydropyridine-2-carboxylate (2.0 g, 9.70 mmol) in CH2Cl2 (25 mL) was added trimethyloxonium tetrafluoroborate (2.0 g, 13.52 mmol). The reaction was rinsed down with CH2Cl2 and stirred at RT for 24 hr. (The reaction eventually cleared up.) To the reaction was added 1N NaOH (75 mL). After stirring for 10 minutes the mixture was poured into a separatory funnel. The CH2Cl2 phase was removed, dried (Na2SO4), filtered and concentrated under vacuum. Purification by silica gel chromatography (Analogix SF25-40 g, 50 to 100% CH2Cl2 in hexanes) gave the product ethyl 5-cyano-6-methoxy-4-methylpicolinate (1.13 g, 5.13 mmol, 52.9% yield) as a white solid. 1H NMR (400 MHz, DMSO-d6) δ 7.75 (s, 1H), 4.37 (q, J=7.1 Hz, 2H), 4.03 (s, 3H), 2.55 (s, 3H), 1.33 (t, J=7.2 Hz, 3H). MS (ES)+m/e 221.2 [M+H]+.

Workup

  1. washThe reaction was rinsed down with CH2Cl2
  2. custom(The reaction
  3. stirringAfter stirring for 10 minutes the mixture
  4. additionwas poured into a separatory funnel
  5. customThe CH2Cl2 phase was removed
  6. dry with materialdried (Na2SO4)
  7. filtrationfiltered
  8. concentrationconcentrated under vacuum
  9. customPurification by silica gel chromatography (Analogix SF25-40 g, 50 to 100% CH2Cl2 in hexanes)

Sources & evidence

ORD record
ord-4b05ac5603cb4e539fbbd7027a79c093
Source dataset
uspto-grants-2013_09
Patent number
US08536179B2

Linked notes

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