Binap, (A+-)- → [(R)-1-(4-Chloro-3-methyl-phenyl)-propyl]-(4-[1,3]dioxolan-2-yl-5-fluoro-pyridin-2-yl)-amine

HRID 1629739ノート

反応式

HRID 1629739 の反応式
Br[C:2]1[CH:7]=[C:6]([CH:8]2[O:12][CH2:11][CH2:10][O:9]2)[C:5]([F:13])=[CH:4][N:3]=1.Cl.[Cl:15][C:16]1[CH:21]=[CH:20][C:19]([C@H:22]([NH2:25])[CH2:23][CH3:24])=[CH:18][C:17]=1[CH3:26].CC(C)([O-])C.[Na+].C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1>C1(C)C=CC=CC=1.CCOC(C)=O.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.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[Cl:15][C:16]1[CH:21]=[CH:20][C:19]([C@H:22]([NH:25][C:2]2[CH:7]=[C:6]([CH:8]3[O:12][CH2:11][CH2:10][O:9]3)[C:5]([F:13])=[CH:4][N:3]=2)[CH2:23][CH3:24])=[CH:18][C:17]=1[CH3:26]

参加物

8

反応物 4

HCID 634876Binap, (A+-)-HCID 23676156Sodium t-butoxideHCID 57517333(R)-1-(4-chloro-3-methyl-phenyl)-propylamine hydrochlorideHCID 575173372-Bromo-4-[1,3]dioxolan-2-yl-5-fluoro-pyridine

生成物 1

HCID 67343197[(R)-1-(4-Chloro-3-methyl-phenyl)-propyl]-(4-[1,3]dioxolan-2-yl-5-fluoro-pyridin-2-yl)-amine

試薬・触媒・溶媒 3

HCID 9811564Bis(dibenzylideneacetone)palladium触媒HCID 1140Toluene溶媒HCID 8857Ethyl Acetate溶媒

反応条件

温度
80 °C

実験手順

To a solution of INT 44 (370 mg, 1.492 mmol), (R)-1-(4-chloro-3-methyl-phenyl)-propylamine hydrochloride (394 mg, 1.790 mmol) and sodium tert-butoxide (344 mg, 3.58 mmol) in degassed toluene (5.8 mL) was added Pd2(dba)3 (68.3 mg, 0.075 mmol) and BINAP (93 mg, 0.149 mmol) and the resulting mixture was stirred at 80° C. for 5 hours. The mixture was diluted in EtOAc, washed with saturated aqueous sodium bicarbonate, water and brine, dried over sodium sulfate, filtered and concentrated. The crude product was purified by flash chromatography on silica gel (cyclohexane/EtOAc) to give INT 46.

後処理

  1. washwashed with saturated aqueous sodium bicarbonate, water and brine
  2. dry with materialdried over sodium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customThe crude product was purified by flash chromatography on silica gel (cyclohexane/EtOAc)
  6. customto give INT 46

出典と根拠

ORDレコード
ord-733d0fab43044471a52be03fcc9d6444
出典データセット
uspto-grants-2014_07
特許番号
US08791100B2

反応ノート

読み込み中…