Toluene → 4-Chloro-2-(3-chlorophenyl)-6-cyclopropylpyridine

HRID 1508807ノート

反応式

HRID 1508807 の反応式
Cl[C:2]1[CH:7]=[C:6]([Cl:8])[CH:5]=[C:4]([CH:9]2[CH2:11][CH2:10]2)[N:3]=1.[Cl:12][C:13]1[CH:14]=[C:15](B(O)O)[CH:16]=[CH:17][CH:18]=1.C([O-])([O-])=O.[Cs+].[Cs+].C1(C)C=CC=CC=1>O.ClCCl.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.CCO>[Cl:8][C:6]1[CH:5]=[C:4]([CH:9]2[CH2:11][CH2:10]2)[N:3]=[C:2]([C:17]2[CH:16]=[CH:15][CH:14]=[C:13]([Cl:12])[CH:18]=2)[CH:7]=1

参加物

9

反応物 4

HCID 1140TolueneHCID 10796Cesium carbonateHCID 2734323(3-Chlorophenyl)boronic acidHCID 901122042,4-Dichloro-6-cyclopropylpyridine

生成物 1

HCID 901124124-Chloro-2-(3-chlorophenyl)-6-cyclopropylpyridine収率 20%

試薬・触媒・溶媒 4

HCID 178418397HCID 178418397、化合物触媒HCID 702Ethanol溶媒HCID 962Water溶媒2 回HCID 6344Dichloromethane溶媒

反応条件

温度
90 °C

実験手順

A 250-mL round bottomed flask was charged with 2,4-dichloro-6-cyclopropylpyridine (1.08 g, 5.74 mmol), (3-chlorophenyl)boronic acid (0.99 g, 6.32 mmol), tetrakis(triphenylphosphine)palladium(0) (0.332 g, 0.28 mmol), and Cs2CO3 (5.61 g, 17.2 mmol). Toluene (40 ml), EtOH (10 ml) and water (20 ml) were added. The resulting mixture was stirred under Ar at 90° C. for 23 h. After cooling to room temperature, the reaction mixture was diluted with water (50 mL) and dichloromethane (50 mL). The mixture was filtered through celite washing solids with dichloromethane. The aqueous layer was separated and extracted with dichloromethane (2×50 mL). The combined organic extract was washed with saturated sodium chloride (25 mL) then dried over sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by chromatography on silica using hexane/dichloromethane (100:0 to 0:100) as eluent to afford the title compound (0.30 g, 20%) as a colorless oil. MW=264.15. 1H NMR (CDCl3, 500 MHz) δ 7.98-7.96 (m, 1H), 7.85-7.80 (m, 1H), 7.45 (d, J=1.5 Hz, 1H), 7.39-7.35 (m, 2H), 7.12 (d, J=1.5 Hz, 1H), 2.18-2.01 (m, 1H), 1.18-1.12 (m, 2H), 1.06-1.00 (m, 2H).

後処理

  1. temperatureAfter cooling to room temperature
  2. filtrationThe mixture was filtered
  3. washthrough celite washing solids with dichloromethane
  4. customThe aqueous layer was separated
  5. extractionextracted with dichloromethane (2×50 mL)
  6. extractionThe combined organic extract
  7. washwas washed with saturated sodium chloride (25 mL)
  8. dry with materialthen dried over sodium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated under reduced pressure
  11. customThe residue was purified by chromatography on silica

出典と根拠

ORDレコード
ord-4d7872c27ac54367849cbdacd34b836c
出典データセット
uspto-grants-2015_12
特許番号
US09221843B2

反応ノート

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