Acetyl chloride → 4-Amino-6-(4-chloro-2-fluoro-3-methoxyphenyl)-3-methyl-pyridine-2-carboxylic acid methyl ester

HRID 506468Notes

Reaction equation

HRID 506468 reaction equation
[CH3:1][O:2][C:3]([C:5]1[C:10]([CH3:11])=[C:9]([NH:12]C(=O)C)[CH:8]=[C:7]([C:16]2[CH:21]=[CH:20][C:19]([Cl:22])=[C:18]([O:23][CH3:24])[C:17]=2[F:25])[N:6]=1)=[O:4].C(Cl)(=O)C>CO>[CH3:1][O:2][C:3]([C:5]1[C:10]([CH3:11])=[C:9]([NH2:12])[CH:8]=[C:7]([C:16]2[CH:21]=[CH:20][C:19]([Cl:22])=[C:18]([O:23][CH3:24])[C:17]=2[F:25])[N:6]=1)=[O:4]

Participants

4

Reactant 2

HCID 6367Acetyl chlorideHCID 594321274-Acetylamino-6-(4-chloro-2-fluoro-3-methoxyphenyl)-3-methylpyridine-2-carboxylic acid methyl ester

Product 1

HCID 594321084-Amino-6-(4-chloro-2-fluoro-3-methoxyphenyl)-3-methyl-pyridine-2-carboxylic acid methyl esterYield 89.9%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

4-Acetylamino-6-(4-chloro-2-fluoro-3-methoxyphenyl)-3-methylpyridine-2-carboxylic acid methyl ester (369 mg, 1.0 mmol) was dissolved in methanol (10 mL) and acetyl chloride (1.07 mL, 15 mmol) was added. The reaction mixture was stirred overnight at ambient temperature and concentrated under vacuum. The residue was partitioned between ethyl acetate and aqueous sodium bicarbonate; and the organic phase was dried and concentrated. Purification by flash chromatography on silica gel (dichloromethane/ethyl acetate gradient) followed by a second purification by flash chromatography (hexane/ethyl acetate gradient) yielded the title compound (292 mg, 88% yield) as a white solid, mp 122-125° C. 1H NMR (CDCl3) δ 7.65 (m, 1H), 7.26 (s, 1H), 7.1 (m, 1H), 4.35 (br s, 2H), 3.99 (s, 3H), 3.98 (d, 3H), 2.31 (s, 3H).

Workup

  1. concentrationconcentrated under vacuum
  2. customThe residue was partitioned between ethyl acetate and aqueous sodium bicarbonate
  3. customand the organic phase was dried
  4. concentrationconcentrated
  5. customPurification by flash chromatography on silica gel (dichloromethane/ethyl acetate gradient)
  6. customfollowed by a second purification by flash chromatography (hexane/ethyl acetate gradient)

Sources & evidence

ORD record
ord-f5ccce6cc3e34b5aa2f647a9870c58ab
Source dataset
uspto-grants-2010_08
Patent number
US07786044B2

Reaction notes

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