Sodium Hydroxide → 5'-(4-Cyano-3-fluorophenyl)-spiro[cyclohexane-1,3'-[3H]indol]-2'(1'H)-one

HRID 396252

Reaction equation

HRID 396252 reaction equation
[C:1]([C:3]1[CH:8]=[CH:7][C:6](Br)=[CH:5][C:4]=1[F:10])#[N:2].[NH:11]1[C:19]2[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=2)[C:13]2([CH2:24][CH:23](B(O)O)[CH2:22][CH2:21][CH2:20]2)[C:12]1=[O:28].C([O-])(=O)C.[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:1]([C:3]1[CH:8]=[CH:7][C:6]([C:16]2[CH:15]=[C:14]3[C:19](=[CH:18][CH:17]=2)[NH:11][C:12](=[O:28])[C:13]23[CH2:24][CH2:23][CH2:22][CH2:21][CH2:20]2)=[CH:5][C:4]=1[F:10])#[N:2]

Participants

8

Reactant 4

HCID 14798Sodium HydroxideHCID 517045Sodium AcetateHCID 7360294-Bromo-2-fluorobenzonitrileHCID 21986219(spiro[cyclohexane-1,3'-[3H]indol]-2'(1'H)-one-5-yl)boronic acid

Product 1

HCID 220193465'-(4-Cyano-3-fluorophenyl)-spiro[cyclohexane-1,3'-[3H]indol]-2'(1'H)-oneYield 37%

Reagents, catalysts & solvents 3

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

Procedure

A solution of 4-cyano-3-fluoro-bromobenzene (0.76 g, 3.8 mmol), and tetrakis(triphenylphosphine)palladium(0) (0.3 g) in ethylene glycol dimethyl ether (15 cm3) was stirred under N2 for 20 minutes. To this mixture was then added (spiro[cyclohexane-1,3′-[3H]indol]-2′(1′H)-one-5-yl)boronic acid (1.4 g, 5.7 mmol) and sodium acetate (1.2 g, 11.4 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 (0.45 g, 37%) as an off-white solid. mp: 258-260° C.; 1H NMR (DMSO-d6) δ 8.8 (s, 1H), 7.7-7.6 (m, 2H), 7.5 (td, 2H, J=0.9. 1.5, 5.7 Hz), 7.4 (dd, 1H, J=1.5, 8.8 Hz), 7.0 (d, 1H, J=8.1 Hz), 2.0-1.6 (m, 10H); MS (−)APCI [M−H]− @ m/z 319.

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-f3daf5465634415a8a19a681c1aa3d72
Source dataset
uspto-grants-2003_08
Patent number
US06608068B2

Linked notes

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