Oxalyl chloride → 6-(4-Fluorophenyl)-2-methyl-3-pyridinecarbonyl chloride

HRID 644706Notes

Reaction equation

HRID 644706 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:13]=[C:12]([CH3:14])[C:11]([C:15]([OH:17])=O)=[CH:10][CH:9]=2)=[CH:4][CH:3]=1.C(Cl)(=O)C([Cl:21])=O>C(Cl)Cl.CN(C=O)C>[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:13]=[C:12]([CH3:14])[C:11]([C:15]([Cl:21])=[O:17])=[CH:10][CH:9]=2)=[CH:4][CH:3]=1

Participants

5

Reactant 2

HCID 65578Oxalyl chlorideHCID 242777906-(4-Fluorophenyl)-2-methylpyridine-3-carboxylic acid

Product 1

HCID 866181086-(4-Fluorophenyl)-2-methyl-3-pyridinecarbonyl chlorideYield 41.6%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideCatalystHCID 6344DichloromethaneSolvent

Conditions

Temperature
40 °C

Procedure

6-(4-Fluorophenyl)-2-methyl-3-pyridinecarboxylic acid (0.2 g, 0.866 mol) was suspended in DCM (14 mL) and DMF (1 drop) was added. The mixture was cooled in an ice-bath and oxalyl chloride (0.226 mL, 2.598 mmol) was added portion wise over 5 minutes. The mixture was heated to 40° C. for 90 minutes. The mixture was allowed to cool and the solvent removed under vacuum to give 6-(4-fluorophenyl)-2-methyl-3-pyridinecarbonyl chloride as a yellow solid (0.270 g) which was used directly in step 2. Step 2: The acid chloride from step 1 was taken up in DCM (3 mL) and added to a solution of 1,1-dimethylethyl (2R,6S)-2,6-dimethyl-4-{[4-(methylamino)phenyl]methyl}-1-piperazinecarboxylate (D9) (0.23 g, 0.693 mmol) in DCM (2 mL). Triethylamine (0.193 mL, 1.386 mmol) was added and the mixture was stirred overnight at room temperature. The reaction mixture was diluted with DCM and washed with water. The aqueous layer was re-extracted with DCM (×2) and the combined organics were dried and concentrated. The crude product was purified by column chromatography. Elution with 0-50% EtOAc/petroleum yielded the title compound as a white foam (0.331 g). δH (CDCl3, 400 MHz) 7.89 (2H, m), 7.36 (1H, m), 7.26 (1H, m), 7.19 (2H, m), 7.10 (2H, t), 6.99 (2H, m), 4.00 (2H, m), 3.53 (3H, s), 3.34 (2H, s), 2.58 (3H, s), 2.44 (2H, d), 2.05 (2H, m), 1.44 (9H, s), 1.18 (6H, d). MS (ES): MH+ 547.3. Description 16

Workup

  1. temperatureThe mixture was cooled in an ice-bath
  2. temperatureto cool
  3. customthe solvent removed under vacuum

Sources & evidence

ORD record
ord-7c91153290cb4778944d0cb0e9b706b3
Source dataset
uspto-grants-2010_04
Patent number
US07700599B2

Reaction notes

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