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

HRID 2386141Notes

Reaction equation

HRID 2386141 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-e5cb6aa35ce34e3f8dfbc6b2b67db3bd
Source dataset
uspto-grants-2012_09
Patent number
US08268753B2

Reaction notes

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