Reaction #66067

Reaction equation

product

7-bromo-3,4,5,6-tetrahydro-1H-2,5-ethanoazepino[4,3-b]indole

trans-2-(4-chlorophenyl)vinylboronic acid

sodium carbonate

→

title compound

7-[(E)-2-(4-chlorophenyl)vinyl]-3,4,5,6-tetrahydro-1H-2,5-ethanoazepino[4,3-b]indole

Solvents

2-propanol

Conditions

Workup

1. 1
   Otherwas purged with nitrogen
2. 2
   TemperatureThe reaction mixture was cooled
3. 3
   Otherpartitioned between CHCl3/2-propanol (4:1, 2×20 mL) and 1.0 M sodium carbonate (30 mL)
4. 4
   DryingThe combined organic extracts were dried (sodium sulfate)
5. 5
   Concentrationconcentrated under vacuum
6. 6
   OtherThe resulting residue was purified by reverse-phase HPLC [Waters XBridge™ RP18 column, 5 μm, 30×100 mm, flow rate 40 mL/minute, 40-99% gradient of methanol in buffer (0.1 M aqueous ammonium bicarbonate, adjusted to pH 10 with ammonium hydroxide)]

Procedure

A suspension of the product of Example 1B (55 mg, 0.19 mmol), trans-2-(4-chlorophenyl)vinylboronic acid (41 mg, 0.23 mmol; Aldrich), dichlorobis(triphenylphosphine)palladium (II) (6.6 mg, 9.4 μmmol; Aldrich) and 1.0 M sodium carbonate (0.47 mL) in 2-propanol (1.5 mL) was purged with nitrogen and then stirred at 110° C. for 5 hours in a sealed tube. The reaction mixture was cooled and partitioned between CHCl3/2-propanol (4:1, 2×20 mL) and 1.0 M sodium carbonate (30 mL). The combined organic extracts were dried (sodium sulfate) and concentrated under vacuum. The resulting residue was purified by reverse-phase HPLC [Waters XBridge™ RP18 column, 5 μm, 30×100 mm, flow rate 40 mL/minute, 40-99% gradient of methanol in buffer (0.1 M aqueous ammonium bicarbonate, adjusted to pH 10 with ammonium hydroxide)] to afford the title compound: 1H NMR (500 MHz, methanol-d4 ) δ ppm 2.03-2.16 (m, 4 H), 3.04-3.12 (m, 2 H), 3.12-3.18 (m, 1 H), 3.20-3.29 (m, 2 H), 4.24 (s, 2 H), 7.01 (t, J=7.6 Hz, 1 H), 7.19-7.26 (m, 2 H), 7.31-7.41 (m, 3 H), 7.55-7.67 (m, 3 H); MS (APCI) m/z 349 (M+H)+.

Source