Thionyl Chloride → 6-[(4-Fluorophenyl)oxy]-3-pyridinecarbonyl chloride

HRID 644707노트

반응식

HRID 644707 반응식
[F:1][C:2]1[CH:7]=[CH:6][C:5]([O:8][C:9]2[N:14]=[CH:13][C:12]([C:15]([OH:17])=O)=[CH:11][CH:10]=2)=[CH:4][CH:3]=1.S(Cl)([Cl:20])=O>O1CCOCC1>[F:1][C:2]1[CH:7]=[CH:6][C:5]([O:8][C:9]2[N:14]=[CH:13][C:12]([C:15]([Cl:20])=[O:17])=[CH:11][CH:10]=2)=[CH:4][CH:3]=1

참가 물질

4

반응물 2

HCID 24386Thionyl ChlorideHCID 167905786-(4-Fluorophenoxy)pyridine-3-carboxylic acid

생성물 1

HCID 231490426-[(4-Fluorophenyl)oxy]-3-pyridinecarbonyl chloride수율 100.7%

시약·촉매·용매 1

HCID 312751,4-Dioxane용매

실험 절차

6-[(4-Fluorophenyl)oxy]-3-pyridinecarboxylic acid (D14) (0.232 g, 0.994 mmol) was dissolved in 1,4-dioxane (6 mL) and thionyl chloride (0.363 mL, 4.972 mmol) added dropwise. The mixture was heated at reflux for 3.5 h, then cooled and concentrated in vacuo. DCM was added to the residue which was then re-concentrated to yield 6-[(4-fluorophenyl)oxy]-3-pyridinecarbonyl chloride as a yellow oil (0.252 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 1,1-dimethylethyl (2S)-2-methyl-4-{[4-(methylamino)phenyl]methyl}-1-piperazinecarboxylate (D3) (0.288 g, 0.904 mmol) in DCM (3 mL). Triethylamine (0.251 mL, 1.808 mmol) was added and the mixture was stirred at room temperature overnight. The reaction mixture was diluted with DCM and washed with water. The aqueous was extracted with DCM (×2) and the combined organic layers were dried and concentrated. The crude product was purified by column chromatography. Elution with a 0-50% EtOAc/petroleum ether gradient gave the title compound as a colourless oil (0.518 g). δH (CDCl3, 400 MHz) 8.07 (1H, m), 7.65 (1H, dd), 7.24 (2H, d), 7.03 (6H, m), 6.70 (1H, d), 4.18 (1H, br.s), 3.80 (1H, d), 3.48 (3H, s), 3.46 (1H, d), 3.34 (1H, d), 3.08 (1H, td), 2.70 (1H, d), 2.50 (1H, d), 2.10 (1H, dd), 2.00 (1H, m), 1.46 (9H, s), 1.20 (3H, d). MS (ES): MH+ 535.3. Description 16: Alternative Method (A)

후처리

  1. temperatureThe mixture was heated
  2. temperatureat reflux for 3.5 h
  3. temperaturecooled
  4. concentrationconcentrated in vacuo
  5. additionDCM was added to the residue which
  6. concentrationwas then re-concentrated

출처 및 근거

ORD 기록
ord-7238d3dd9ff64233b36804e4a8133fa8
출처 데이터셋
uspto-grants-2010_04
특허 번호
US07700599B2

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