Thionyl Chloride → 6-(3-Fluorophenyl)-3-pyridinecarbonyl chloride

HRID 644715Notes

Reaction equation

HRID 644715 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([C:8]2[N:13]=[CH:12][C:11]([C:14]([OH:16])=O)=[CH:10][CH:9]=2)[CH:5]=[CH:6][CH:7]=1.S(Cl)([Cl:19])=O>O1CCOCC1>[F:1][C:2]1[CH:3]=[C:4]([C:8]2[N:13]=[CH:12][C:11]([C:14]([Cl:19])=[O:16])=[CH:10][CH:9]=2)[CH:5]=[CH:6][CH:7]=1

Participants

4

Reactant 2

HCID 24386Thionyl ChlorideHCID 247299726-(3-Fluorophenyl)nicotinic acid

Product 1

HCID 866181106-(3-Fluorophenyl)-3-pyridinecarbonyl chlorideYield 99.3%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

6-(3-Fluorophenyl)-3-pyridinecarboxylic acid (82 mg, 0.376 mmol) was stirred in dioxane (4 mL) and thionyl chloride (0.137 mL, 1.88 mmol) added dropwise. The reaction mixture was heated at reflux for 40 min then concentrated in vacuo to give 6-(3-fluorophenyl)-3-pyridinecarbonyl chloride as a white solid (0.088 g) which was used directly in step 2. Step 2: The acid chloride from step 1 was taken up in DCM and added drop-wise to a mixture of 1,1-dimethylethyl (2S)-2-methyl-4-{[4-(methylamino)phenyl]methyl}-1-piperazinecarboxylate (D3) (0.1 g, 0.313 mmol) and triethylamine (0.065 mL, 0.47 mmol) in DCM (5 mL). The reaction mixture was stirred at room temperature under argon for ˜15 h, then diluted with water and DCM. The organic layer was dried and concentrated to give the crude product, which was purified by column chromatography. Elution with EtOAc/petroleum ether yielded the title compound as a yellow oil (0.127 g). δH (CDCl3, 400 MHz) 8.51 (1H, d), 7.75 (1H, dd), 7.67 (2H, m), 7.55 (1H, d), 7.40 (1H, m), 7.24 (2H, d), 7.08 (1H, m), 7.03 (2H, d), 4.15 (1H, br.s), 3.78 (1H, d), 3.53 (3H, s), 3.45 (1H, d), 3.32 (1H, d), 3.06 (1H, td), 2.69 (1H, d), 2.49 (1H, d), 2.09 (1H, dd), 1.98 (1H, m), 1.44 (9H, s), 1.16 (3H, d). MS (ES): MH+ 519.3. Description 61

Workup

  1. temperatureThe reaction mixture was heated
  2. temperatureat reflux for 40 min
  3. concentrationthen concentrated in vacuo

Sources & evidence

ORD record
ord-7aa3d7a6f4a04709bb2846816954e23f
Source dataset
uspto-grants-2010_04
Patent number
US07700599B2

Reaction notes

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