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

HRID 37789

Reaction equation

HRID 37789 reaction equation
Br[C:2]1[C:10]2[NH:9][C:8]3[CH:11]4[CH2:17][CH2:16][N:14]([CH2:15][C:7]=3[C:6]=2[CH:5]=[CH:4][CH:3]=1)[CH2:13][CH2:12]4.[Cl:18][C:19]1[CH:24]=[CH:23][C:22](/[CH:25]=[CH:26]/B(O)O)=[CH:21][CH:20]=1.C(=O)([O-])[O-].[Na+].[Na+]>CC(O)C.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[Cl:18][C:19]1[CH:24]=[CH:23][C:22](/[CH:25]=[CH:26]/[C:2]2[C:10]3[NH:9][C:8]4[CH:11]5[CH2:17][CH2:16][N:14]([CH2:15][C:7]=4[C:6]=3[CH:5]=[CH:4][CH:3]=2)[CH2:13][CH2:12]5)=[CH:21][CH:20]=1

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 642694trans-2-(4-Chlorophenyl)vinylboronic acidHCID 672401637-bromo-3,4,5,6-tetrahydro-1H-2,5-ethanoazepino[4,3-b]indole

Product 1

HCID 532509317-[(E)-2-(4-chlorophenyl)vinyl]-3,4,5,6-tetrahydro-1H-2,5-ethanoazepino[4,3-b]indole

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalystHCID 3776IsopropanolSolvent

Conditions

Temperature
110 °C

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)+.

Workup

  1. customwas purged with nitrogen
  2. temperatureThe reaction mixture was cooled
  3. custompartitioned between CHCl3/2-propanol (4:1, 2×20 mL) and 1.0 M sodium carbonate (30 mL)
  4. dry with materialThe combined organic extracts were dried (sodium sulfate)
  5. concentrationconcentrated under vacuum
  6. customThe 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)]

Sources & evidence

ORD record
ord-bcadcd0cca984b508ef42d3b9906d070
Source dataset
uspto-grants-2013_09
Patent number
US08524703B2

Linked notes

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