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

HRID 1508807노트

반응식

HRID 1508807 반응식
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

참가 물질

9

반응물 4

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

생성물 1

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

시약·촉매·용매 4

HCID 178418397HCID 178418397, 화합물촉매HCID 702Ethanol용매HCID 962Water용매2회HCID 6344Dichloromethane용매

반응 조건

온도
90 °C

실험 절차

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).

후처리

  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

출처 및 근거

ORD 기록
ord-4d7872c27ac54367849cbdacd34b836c
출처 데이터셋
uspto-grants-2015_12
특허 번호
US09221843B2

반응 노트

불러오는 중…