Cesium carbonate → 1-(3-(1,3-Dioxolan-2-yl)-5-(trifluoromethoxy)phenyl)-4-isopropylpiperazine

HRID 1519436Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1519436
Br[C:2]1[CH:3]=[C:4]([CH:13]2[O:17][CH2:16][CH2:15][O:14]2)[CH:5]=[C:6]([O:8][C:9]([F:12])([F:11])[F:10])[CH:7]=1.[CH:18]([N:21]1[CH2:26][CH2:25][NH:24][CH2:23][CH2:22]1)([CH3:20])[CH3:19].C1(P(C2C=CC=CC=2)C2C=CC3C(=CC=CC=3)C=2C2C3C(=CC=CC=3)C=CC=2P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C(=O)([O-])[O-].[Cs+].[Cs+]>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].C1(C)C=CC=CC=1>[O:14]1[CH2:15][CH2:16][O:17][CH:13]1[C:4]1[CH:3]=[C:2]([N:24]2[CH2:25][CH2:26][N:21]([CH:18]([CH3:20])[CH3:19])[CH2:22][CH2:23]2)[CH:7]=[C:6]([O:8][C:9]([F:12])([F:11])[F:10])[CH:5]=1

Komponenten

7

Edukt 4

HCID 10796Cesium carbonateHCID 780131-IsopropylpiperazineHCID 634876Binap, (A+-)-HCID 867193482-[3-Bromo-5-(trifluoromethoxy)phenyl]-1,3-dioxolane

Produkt 1

HCID 867193491-(3-(1,3-Dioxolan-2-yl)-5-(trifluoromethoxy)phenyl)-4-isopropylpiperazineAusbeute 70 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 9811564Bis(dibenzylideneacetone)palladiumKatalysatorHCID 1140TolueneLösungsmittel

Reaktionsbedingungen

Temperatur
100 °C

Versuchsvorschrift

Tris(dibenzylideneacetone)dipalladium(0) (363 mg, 0.396 mmol) was added to a suspension of 2-(3-bromo-5-(trifluoromethoxy)phenyl)-1,3-dioxolane (21, 1.24 g, 3.96 mmol), isopropylpiperazine (610 mg, 4.75 mmol), racemic-2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (rac-BINAP, 345 mg, 0.554 mmol), cesium carbonate (2.58 g, 7.92 mmol) and anhydrous toluene (50 mL). The mixture was placed under nitrogen and heated to 100° C. for 17 h. The solvent was removed in vacuo and methanol (30 mL) and silica gel (30 g) were added. After removing the methanol the adsorbed crude product was purified by silica gel chromatography eluting with 0-60% EtOAc in hexanes to afford the title compound (996 mg, 70%) as an orange oil: 1H NMR (500 MHz, CDCl3) δ 6.93 (s, 1H), 6.78 (s, 1H), 6.68 (s, 1H), 5.77 (s, 1H), 4.17-3.99 (m, 4H), 3.26-3.22 (m, 4H), 2.72 (sept, 1H), 2.68-2.62 (m, 4H), 1.08 (d, J=6.5 Hz, 6H).

Aufarbeitung

  1. customThe solvent was removed in vacuo and methanol (30 mL) and silica gel (30 g)
  2. additionwere added
  3. customAfter removing the methanol the adsorbed crude product
  4. customwas purified by silica gel chromatography
  5. washeluting with 0-60% EtOAc in hexanes

Quellen und Nachweise

ORD-Eintrag
ord-3a22c274916440edb5427793ee563c08
Quelldatensatz
uspto-grants-2015_07
Patentnummer
US09073878B2

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