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

HRID 1629739노트

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HRID 1629739 반응식
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]

참가 물질

8

반응물 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

생성물 1

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

시약·촉매·용매 3

HCID 9811564Bis(dibenzylideneacetone)palladium촉매HCID 1140Toluene용매HCID 8857Ethyl Acetate용매

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온도
80 °C

실험 절차

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.

후처리

  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

출처 및 근거

ORD 기록
ord-733d0fab43044471a52be03fcc9d6444
출처 데이터셋
uspto-grants-2014_07
특허 번호
US08791100B2

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