Phosphorus oxychloride → Ethyl 6-chloro-2-(2,4-difluorophenyl)pyridine-3-carboxylate

HRID 1257092ノート

反応式

HRID 1257092 の反応式
[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C:9]1[C:14]([C:15]([O:17][CH2:18][CH3:19])=[O:16])=[CH:13][CH:12]=[CH:11][N+:10]=1[O-].P(Cl)(Cl)([Cl:23])=O>ClC(Cl)C>[Cl:23][C:11]1[CH:12]=[CH:13][C:14]([C:15]([O:17][CH2:18][CH3:19])=[O:16])=[C:9]([C:3]2[CH:4]=[CH:5][C:6]([F:8])=[CH:7][C:2]=2[F:1])[N:10]=1

参加物

4

反応物 2

HCID 24813Phosphorus oxychlorideHCID 582235643-Pyridinecarboxylic acid, 2-(2,4-difluorophenyl)-, ethyl ester, 1-oxide2 回

生成物 1

HCID 21062879Ethyl 6-chloro-2-(2,4-difluorophenyl)pyridine-3-carboxylate

試薬・触媒・溶媒 1

HCID 63651,1-Dichloroethane溶媒

反応条件

温度
72.5 °C

実験手順

To a nitrogen purged 500 mL, 3-necked flask, fitted with a reflux condenser, heating mantle and a thermocouple was charged 2-(2,4-difluorophenyl)-3-(ethoxycarbonyl)pyridine 1-oxide, 4 (21 g, 75 mmoles, 1.0 eq), followed by 150 mL dichloroethane. Phosphorous oxychloride (75 mL) was added in one aliquate with stirring, causing an immediate rise in temperature from 21 to 23° C. followed by gradual warming. The solution was heated under nitrogen to 70-75° C. (completeness of reaction determined by HPLC). The reaction was then cooled to room temperature and concentrated under vacuum to remove most of the POCl3. The remainder was quenched by slowly pouring onto 450 g of ice. The mixture (after the ice melted) was then extracted into methylene chloride (2×200 mL). The combined organics were dried (MgSO4), filtered through silica, eluted with methylene chloride, and concentrated to give the title Compound, 5, as an orange solid. 1H NMR (500.0 MHz, CDCl3) d 8.15 (d, J=8.2 Hz, 1H), 7.54 (td, J=8.5, 5.0 Hz, 1H), 7.34 (d, J=8.2 Hz, 1H), 6.96-6.92 (m, 1H), 6.79-6.74 (m, 1H), 4.16 (q, J=7.2 Hz, 2H), 1.10 (t, J=7.1 Hz, H) ppm.

後処理

  1. customTo a nitrogen purged 500 mL, 3-necked flask
  2. customfitted with a reflux condenser
  3. temperatureheating mantle
  4. customfrom 21 to 23° C.
  5. custom(completeness of reaction determined by HPLC)
  6. temperatureThe reaction was then cooled to room temperature
  7. concentrationconcentrated under vacuum
  8. customto remove most of the POCl3
  9. customThe remainder was quenched
  10. additionby slowly pouring onto 450 g of ice
  11. extractionwas then extracted into methylene chloride (2×200 mL)
  12. dry with materialThe combined organics were dried (MgSO4)
  13. filtrationfiltered through silica
  14. washeluted with methylene chloride
  15. concentrationconcentrated

出典と根拠

ORDレコード
ord-8e5f0261278d45dbb5c5807affb603bd
出典データセット
uspto-grants-2013_06
特許番号
US08461345B2

反応ノート

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