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

HRID 245293Notes

Reaction equation

HRID 245293 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-0d7eba460f9f411e8450c07a5a702760
Source dataset
uspto-grants-2014_02
Patent number
US08658791B2

Reaction notes

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