Sodium Carbonate → 5'-(3Cyanophenyl)-spiro[cyclopentane-1,3'-[3H]indol]-2'(1'H)-one

HRID 852512Notes

Reaction equation

HRID 852512 reaction equation
Br[C:2]1[CH:3]=[C:4]([CH:7]=[CH:8][CH:9]=1)[C:5]#[N:6].[NH:10]1[C:18]2[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=2)[C:12]2([CH:22](B(O)O)[CH2:21][CH2:20][CH2:19]2)[C:11]1=[O:26].C(=O)([O-])[O-].[Na+].[Na+].[OH-].[Na+]>COCCOC.O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[C:5]([C:4]1[CH:3]=[C:2]([C:15]2[CH:14]=[C:13]3[C:18](=[CH:17][CH:16]=2)[NH:10][C:11](=[O:26])[C:12]23[CH2:22][CH2:21][CH2:20][CH2:19]2)[CH:9]=[CH:8][CH:7]=1)#[N:6]

Participants

8

Reactant 4

HCID 10340Sodium CarbonateHCID 14798Sodium HydroxideHCID 233813-BromobenzonitrileHCID 21986244(spiro[cyclopentane-1,3'-[3H]indol]-2'(1'H)-one-5-yl)boronic acid

Product 1

HCID 99478785'-(3Cyanophenyl)-spiro[cyclopentane-1,3'-[3H]indol]-2'(1'H)-oneYield 40%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 80711,2-DimethoxyethaneSolvent

Procedure

A solution of 3-bromobenzonitrile (0.5 g, 2.6 mmol), and tetrakis(triphenylphosphine)palladium(0) (0.2 g) in ethylene glycol dimethyl ether (20 cm3) was stirred under N2 for 20 minutes. To this mixture was then added (spiro[cyclopentane-1,3′-[3H]indol]-2′(1′H)-one-5-yl) boronic acid (0.9 g, 3.9 mmol) and sodium carbonate (0.8 g, 7.8 mmol) in water (5 cm3). The solution was brought to reflux for 18 hours and then cooled to room temperature, poured into 2N NaOH and extracted with EtOAc (×3). The combined extracts were washed with water, brine, dried (MgSO4), and evaporated. The residue was purified by column chromatography (SiO2, EtOAc, hexane) to afford the title compound (0.30 g, 40%) as an off-white solid. mp: 217-219° C.; 1H NMR (DMSO-d6) δ 10.4 (s, 1H), 8.2 (s, 1H), 8.0 (d, 1H, J=8.1 Hz), 7.8 (d, 1H, J=7.7 Hz), 7.6 (m, 2H), 7.5 (dd, 1H, J=1.8, 6.3 Hz), 6.9 (d, 1H, J=8.1 Hz), 2.0-1.9 (m, 8H); MS [M−H]−=287.

Workup

  1. temperatureto reflux for 18 hours
  2. extractionextracted with EtOAc (×3)
  3. washThe combined extracts were washed with water, brine
  4. dry with materialdried (MgSO4)
  5. customevaporated
  6. customThe residue was purified by column chromatography (SiO2, EtOAc, hexane)

Sources & evidence

ORD record
ord-0291cb178648424f8e66c0639a939eb1
Source dataset
uspto-grants-2007_08
Patent number
US07253203B2

Reaction notes

Loading…