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

HRID 644715ノート

反応式

HRID 644715 の反応式
[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

参加物

4

反応物 2

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

生成物 1

HCID 866181106-(3-Fluorophenyl)-3-pyridinecarbonyl chloride収率 99.3%

試薬・触媒・溶媒 1

HCID 312751,4-Dioxane溶媒

実験手順

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

後処理

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

出典と根拠

ORDレコード
ord-7aa3d7a6f4a04709bb2846816954e23f
出典データセット
uspto-grants-2010_04
特許番号
US07700599B2

反応ノート

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