4-Bromo-2-(((2-(5,5-dimethyl-1-cyclopenten-1-yl)-2'-fluoro-5'-(methyloxy)-1,1'-biphenyl-4-yl)methyl)oxy)pyridine → Ethyl 3-(2-(((2-(5,5-dimethyl-1-cyclopenten-1-yl)-2'-fluoro-5'-(methyloxy)-1,1'-biphenyl-4-yl)methyl)oxy)-4-pyridinyl)propanoate

HRID 1662575

反応式

HRID 1662575 の反応式
Br[C:2]1[CH:7]=[CH:6][N:5]=[C:4]([O:8][CH2:9][C:10]2[CH:15]=[CH:14][C:13]([C:16]3[CH:21]=[C:20]([O:22][CH3:23])[CH:19]=[CH:18][C:17]=3[F:24])=[C:12]([C:25]3[C:29]([CH3:31])([CH3:30])[CH2:28][CH2:27][CH:26]=3)[CH:11]=2)[CH:3]=1.[Br-].[CH2:33]([O:35][C:36](=[O:40])[CH2:37][CH2:38][Zn+])[CH3:34]>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].CC(P(C(C)(C)C)[C]1[CH][CH][CH][CH]1)(C)C.C1C=CC([C]2[C](C3C=CC=CC=3)[C](C3C=CC=CC=3)[C](C3C=CC=CC=3)[C]2C2C=CC=CC=2)=CC=1.[Fe].C1COCC1>[CH3:30][C:29]1([CH3:31])[C:25]([C:12]2[CH:11]=[C:10]([CH2:9][O:8][C:4]3[CH:3]=[C:2]([CH2:38][CH2:37][C:36]([O:35][CH2:33][CH3:34])=[O:40])[CH:7]=[CH:6][N:5]=3)[CH:15]=[CH:14][C:13]=2[C:16]2[CH:21]=[C:20]([O:22][CH3:23])[CH:19]=[CH:18][C:17]=2[F:24])=[CH:26][CH2:27][CH2:28]1

参加物

6

反応物 2

HCID 577058284-Bromo-2-(((2-(5,5-dimethyl-1-cyclopenten-1-yl)-2'-fluoro-5'-(methyloxy)-1,1'-biphenyl-4-yl)methyl)oxy)pyridineHCID 178471816HCID 178471816、化合物

生成物 1

HCID 57706923Ethyl 3-(2-(((2-(5,5-dimethyl-1-cyclopenten-1-yl)-2'-fluoro-5'-(methyloxy)-1,1'-biphenyl-4-yl)methyl)oxy)-4-pyridinyl)propanoate収率 78%

試薬・触媒・溶媒 3

HCID 6505921(1E,4E)-1,5-diphenylpenta-1,4-dien-3-one; palladium触媒HCID 178454872HCID 178454872、化合物触媒HCID 8028Tetrahydrofuran溶媒2 回

反応条件

温度
80 °C

実験手順

To a sealed tube containing 95.A (0.1059 g, 0.22 mmol), bis(dibenzylideneacetone)palladium (0.0068 g, 0.012 mmol), and CTC-Q-Phos (commercially available from Strem Chemicals) (0.0079 g, 0.011 mmol) was added dry THF (2.1 mL). After 5 minutes, 3-ethoxy-3-oxopropylzinc bromide, 0.5 M solution in THF (0.9 mL, 0.45 mmol) was added dropwise. After 1 hour, the mixture was heated to 80° C. and monitored with TLC and LC-MS. After 16.5 hours, the reaction was cooled to room temperature, and then the organic solvent was removed under reduced pressure. The solid was filtered off, and the solvent was concentrated. The residue was purified by silica gel flash chromatography (0-40% EtOAc/hexane) to afford 95.B (86.2 mg, 78% yield). 1H NMR (500 MHz) (CDCl3) δ ppm 8.10 (1H, d, J=5.4 Hz), 7.41 (1H, dd, J=7.9, 1.8 Hz), 7.33 (2H, dd, J=4.6, 1.5 Hz), 6.98 (1H, m), 6.81 (3H, m), 6.70 (1H, s), 5.52 (1H, t, J=2.0 Hz), 5.42 (2H, s), 4.15 (2H, q, J=7.1 Hz), 3.76 (3H, s), 2.93 (2H, t, J=7.7 Hz), 2.66 (2H, m), 2.25 (2H, td, J=7.0, 2.4 Hz), 1.66 (2H, t, J=7.0 Hz), 1.25 (3H, t, J=7.1 Hz), 0.86 (6H, s).

後処理

  1. waitAfter 1 hour
  2. waitAfter 16.5 hours
  3. temperaturethe reaction was cooled to room temperature
  4. customthe organic solvent was removed under reduced pressure
  5. filtrationThe solid was filtered off
  6. concentrationthe solvent was concentrated
  7. customThe residue was purified by silica gel flash chromatography (0-40% EtOAc/hexane)

出典と根拠

ORDレコード
ord-c13e7fedcd5e494f9192825e06edb868
出典データセット
uspto-grants-2011_10
特許番号
US08030354B2

関連ノート

読み込み中…