Acetic Anhydride → Methyl 2-acetamidoisonicotinate

HRID 889434Notes

Reaction equation

HRID 889434 reaction equation
[NH2:1][C:2]1[CH:3]=[C:4]([CH:9]=[CH:10][N:11]=1)[C:5]([O:7][CH3:8])=[O:6].[C:12](OC(=O)C)(=[O:14])[CH3:13]>CC(O)=O>[C:12]([NH:1][C:2]1[CH:3]=[C:4]([CH:9]=[CH:10][N:11]=1)[C:5]([O:7][CH3:8])=[O:6])(=[O:14])[CH3:13]

Participants

4

Reactant 2

HCID 7918Acetic AnhydrideHCID 236984Methyl 2-aminopyridine-4-carboxylate

Product 1

HCID 22185175Methyl 2-acetamidoisonicotinateYield 76.9%

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Procedure

To a solution of methyl 2-aminoisonicotinate (0.5 g, 3.29 mmol) in AcOH (6.6 mL) at room temperature was added acetic anhydride (0.37 mL, 3.94 mmol), and the mixture was refluxed for 1 hour. The mixture was cooled and transferred to a 100 mL round-bottom, where the product was precipitated out of solution by slowly adding water (˜6 mL). The suspension was then filtered and washed with water. The solid was dried in vacuo overnight, furnishing Intermediate 62A (0.491 g, 76% yield) as a light yellow solid. HPLC: Rt=1.927 min. (YMC S5 ODS 4.6×50 mm, 10-90% aqueous methanol containing 0.2% H3PO4, 4 min. gradient, monitored at 220 nm). MS (ES): m/z=195.1 [M+H]+. 1H NMR (400 MHz, DMSO-d6) δ ppm 10.76 (1H, s), 8.57 (1H, s), 8.48 (1H, d, J=5.04 Hz), 7.51 (1H, dd, J=5.04, 1.51 Hz), 3.88 (3H, s), 2.11 (3H, s).

Workup

  1. temperaturethe mixture was refluxed for 1 hour
  2. temperatureThe mixture was cooled
  3. customwhere the product was precipitated out of solution by slowly adding water (˜6 mL)
  4. filtrationThe suspension was then filtered
  5. washwashed with water
  6. customThe solid was dried in vacuo overnight

Sources & evidence

ORD record
ord-ca8fc25a117c43aeb662e84cc4430f79
Source dataset
uspto-grants-2012_08
Patent number
US08252795B2

Reaction notes

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