Reaktion #2287961

Reaktionsgleichung

2-[4-(7-bromoquinoxalin-5-yl)oxycyclohexyl]isoindoline-1,3-dione

morpholine

Cs2CO3

rac-BINAP

→

2-((cis)-4-((7-morpholinoquinoxalin-5-yl)oxy)cyclohexyl)isoindoline-1,3-dione

Ausbeute 74.2%

Lösungsmittel

toluene

Reaktionsbedingungen

Aufarbeitung

1. 1
   SonstigeAs shown in step 9-ii of Scheme 9, In a round bottom flask
2. 2
   Sonstigefitted with a condenser
3. 3
   TemperaturAfter cooling to room temperature
4. 4
   Filtrationthe mixture was filtered through diatomaceous earth
5. 5
   Einengenconcentrated under reduced pressure
6. 6
   SonstigeThe residue was triturated with Et2O
7. 7
   Filtrationthe solids collected by filtration
8. 8
   Waschenwashed with Et2O

Vorschrift

As shown in step 9-ii of Scheme 9, In a round bottom flask fitted with a condenser, a mixture of 2-[4-(7-bromoquinoxalin-5-yl)oxycyclohexyl]isoindoline-1,3-dione (6.2 g, 12.34 mmol), morpholine (1.61 g, 1.62 mL, 18.5 mmol), and Cs2CO3 (12.06 g, 37.0 mmol) in anhydrous toluene (73 mL) was treated with rac-BINAP (768.4 mg, 1.234 mmol) and Pd2(dba)3 (565 mg, 0.617 mmol). The reaction mixture was heated at 110° C. for 18 hours. After cooling to room temperature, the mixture was filtered through diatomaceous earth and concentrated under reduced pressure. The residue was triturated with Et2O and the solids collected by filtration and washed with Et2O to produce 2-((cis)-4-((7-morpholinoquinoxalin-5-yl)oxy)cyclohexyl)isoindoline-1,3-dione (compound 1029, 4.2 g) as yellow solid. The filterate was concentrated under reduced pressure and purified by medium pressure silica gel chromatography (0-100% EtOAc/hexanes gradient) to produce an additional 300 mg of compound 1029: 1H-NMR (300 MHz, CDCl3) δ 8.76-8.63 (m, 2H), 7.85 (dd, J=5.4, 3.1 Hz, 2H), 7.79-7.60 (m, 2H), 7.09 (d, J=2.6 Hz, 1H), 6.99 (d, J=2.5 Hz, 1H), 5.06 (t, J=2.8 Hz, 1H), 4.27 (tt, J=12.3, 3.8 Hz, 1H), 4.02-3.85 (m, 4H), 3.49-3.27 (m, 4H), 3.03-2.75 (m, 2H), 2.37 (d, J=14.0 Hz, 2H), 1.83-1.56 (m, 4H).

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