Hydrochloric Acid → 2-(3-Chloro-4-fluoro-phenyl)-1-(6-methyl-pyridin-2-yl)-ethanone

HRID 8224

Reaction equation

HRID 8224 reaction equation
[H-].[Na+].[Cl:3][C:4]1[CH:5]=[C:6]([CH2:11]C#N)[CH:7]=[CH:8][C:9]=1[F:10].CO[C:16]([C:18]1[CH:23]=[CH:22][CH:21]=[C:20]([CH3:24])[N:19]=1)=[O:17].Cl>C(O)C>[Cl:3][C:4]1[CH:5]=[C:6]([CH2:11][C:16]([C:18]2[CH:23]=[CH:22][CH:21]=[C:20]([CH3:24])[N:19]=2)=[O:17])[CH:7]=[CH:8][C:9]=1[F:10]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 24758Sodium hydrideHCID 73022Methyl 6-methylpyridine-2-carboxylateHCID 27737253-Chloro-4-fluorobenzyl cyanide

Product 1

HCID 219926502-(3-Chloro-4-fluoro-phenyl)-1-(6-methyl-pyridin-2-yl)-ethanone

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

A dispersion of sodium hydride, (60% in mineral oil, 0.7 g, 17.7 mmol) is added to ethanol (25 mL). When gas evolution ceases, 3-chloro-4-fluorophenylacetonitrile (Fluorochemicals, 2.0 g, 11.8 mmol) and 6-methyl-pyridine-2-carboxylic acid methyl ester (1.8 g, 11.8 mmol), are added. The mixture is refluxed for 2.5 h and adjusted to pH 7 with 1 N hydrochloric acid. The mixture is concentrated in vacuo. Concentrated hydrochloric acid (50 mL) is added to the mixture after which it is refluxed for 1.5 h. The mixture is poured over ice and adjusted to pH 8 with 5 N sodium hydroxide. The mixture is extracted with methylene chloride and the organic portions dried over anhydrous sodium sulfate. The mixture is filtered and concentrated in vacuo to yield the title compound, 2.1 g (68%), as a yellowish solid.

Workup

  1. temperatureThe mixture is refluxed for 2.5 h
  2. concentrationThe mixture is concentrated in vacuo
  3. additionConcentrated hydrochloric acid (50 mL) is added to the mixture after which it
  4. temperatureis refluxed for 1.5 h
  5. additionThe mixture is poured over ice
  6. extractionThe mixture is extracted with methylene chloride
  7. dry with materialthe organic portions dried over anhydrous sodium sulfate
  8. filtrationThe mixture is filtered
  9. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-6a30b69e3a2e470fa2da2fd96723c11b
Source dataset
uspto-grants-2006_08
Patent number
US07087626B2

Linked notes

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