5-Chloro-3-methyl-1-phenyl-1H-pyrazole → 5-(3-cyclopentyloxy-4-methoxyphenyl)-3-methyl-1-phenyl-1H-pyrazole

HRID 2113692ノート

反応式

HRID 2113692 の反応式
Cl[C:2]1[N:6]([C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=2)[N:5]=[C:4]([CH3:13])[CH:3]=1.C([Li])(C)(C)C.Br[C:20]1[CH:25]=[CH:24][C:23]([O:26][CH3:27])=[C:22]([O:28][CH:29]2[CH2:33][CH2:32][CH2:31][CH2:30]2)[CH:21]=1>C1COCC1.C(OCC)(=O)C.[Cl-].[Zn+2].[Cl-].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>[CH:29]1([O:28][C:22]2[CH:21]=[C:20]([C:2]3[N:6]([C:7]4[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=4)[N:5]=[C:4]([CH3:13])[CH:3]=3)[CH:25]=[CH:24][C:23]=2[O:26][CH3:27])[CH2:30][CH2:31][CH2:32][CH2:33]1

参加物

8

反応物 3

HCID 27357715-Chloro-3-methyl-1-phenyl-1H-pyrazoleHCID 99703924-Bromo-2-(cyclopentyloxy)-1-methoxybenzeneHCID 178418306HCID 178418306、化合物

生成物 1

HCID 114508965-(3-cyclopentyloxy-4-methoxyphenyl)-3-methyl-1-phenyl-1H-pyrazole収率 27.8%

試薬・触媒・溶媒 4

HCID 3007855Zincchloride触媒HCID 178418397HCID 178418397、化合物触媒HCID 8028Tetrahydrofuran溶媒2 回HCID 8857Ethyl Acetate溶媒

反応条件

温度
-78 °C

実験手順

A solution of 5-chloro-3-methyl-1-phenyl-1H-pyrazole (61.8 mg, 0.32 mmol) in 5 mL of THF was cooled to −78° C. and t-butyllithium (0.47 mL, 1.7 M in heptane) was slowly added. The mixture was stirred at −78° C. for 1.5 hours and then zinc chloride (1.56 mL, 0.5 M) was added and after stirring at −78° C. for 15 minutes was warmed to room temperature. A solution containing 4-bromo-2-cyclopentyloxy-1-methoxybenzene (148 mg, 0.54 mmol) and Pd(PPh3)4 (35 mg, 0.03 mmol) in 1 ML of THF was added and the reaction was heated to 60° C. for 12 hours. The mixture was diluted with 20 mL of ethyl acetate and the organic layer was washed with 10 mL of a saturated ammonium chloride solution, 20 mL of water and 20 mL of brine. The organic layer was dried over sodium sulfate, filtered and concentrated. Purification by silica gel column chromatography using a gradient elution from 20% to 50% ethyl acetate in hexanes yielded 31 mg of 5-(3-cyclopentyloxy-4-methoxyphenyl)-3-methyl-1-phenyl-1H-pyrazole. 1H-NMR (CDCl3, 300 MHz) δ 7.3 (m, 5H), 6.8 (m, 2H), 6.6 (d, 1H), 6.3 (s, 1H), 4.4 (m, 1H), 3.8 (s, 3H). 2.4 (s, 3H), 1.7-1.5 (m, 8H). (M+1)=349.1

後処理

  1. stirringafter stirring at −78° C. for 15 minutes
  2. temperaturewas warmed to room temperature
  3. additionwas added
  4. temperaturethe reaction was heated to 60° C. for 12 hours
  5. washthe organic layer was washed with 10 mL of a saturated ammonium chloride solution, 20 mL of water and 20 mL of brine
  6. dry with materialThe organic layer was dried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customPurification by silica gel column chromatography
  10. washa gradient elution from 20% to 50% ethyl acetate in hexanes

出典と根拠

ORDレコード
ord-edaea41a512e4405b5553a070c556b69
出典データセット
uspto-grants-2008_10
特許番号
US07432266B2

反応ノート

読み込み中…