Sodium Carbonate → 4'-Chloro-3,8'-biquinoline

HRID 1403096Notes

Reaction equation

HRID 1403096 reaction equation
Br[C:2]1[CH:3]=[CH:4][CH:5]=[C:6]2[C:11]=1[N:10]=[CH:9][CH:8]=[C:7]2[Cl:12].[N:13]1[C:22]2[C:17](=[CH:18][CH:19]=[CH:20][CH:21]=2)[CH:16]=[C:15](B(O)O)[CH:14]=1.C(=O)([O-])[O-].[Na+].[Na+]>COCCOC.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>[Cl:12][C:7]1[C:6]2[C:11](=[C:2]([C:15]3[CH:14]=[N:13][C:22]4[C:17]([CH:16]=3)=[CH:18][CH:19]=[CH:20][CH:21]=4)[CH:3]=[CH:4][CH:5]=2)[N:10]=[CH:9][CH:8]=1

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 2734663Quinoline-3-boronic acidHCID 124036918-Bromo-4-chloroquinoline

Product 1

HCID 867011504'-Chloro-3,8'-biquinolineYield 41.6%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 80711,2-DimethoxyethaneSolvent

Procedure

Pd(PPh3)4 (0.0581 g) was added to a solution of the obtained 8-bromo-4-chloroquinoline (0.242 g), 3-quinolineboronic acid (0.163 g), and an aqueous sodium carbonate solution (2 M, 1.5 mL) in ethylene glycol dimethyl ether (3.0 mL) in a nitrogen atmosphere, and the mixture was stirred at 85° C. for 3 hours. The reaction solution was partitioned between ethyl acetate and water. The organic layer was washed with brine and then dried over anhydrous sodium sulfate. The solvent was distilled off, and the residue was purified by neutral silica gel column chromatography (chloroform/methanol) to obtain 4′-chloro-3,8′-biquinoline (0.114 g) as a white solid. Compound (117) was obtained as a pale yellow solid (yield based on 6 steps: 37%) according to Example 3(3) using the obtained 4′-chloro-3,8′-biquinoline instead of compound (3b) and 4-cyano-3-(4-hydroxycyclohexylamino)phenylboronic acid pinacol ester instead of 4-cyano-3-(ethylamino)phenylboronic acid pinacol ester.

Workup

  1. customThe reaction solution was partitioned between ethyl acetate and water
  2. washThe organic layer was washed with brine
  3. dry with materialdried over anhydrous sodium sulfate
  4. distillationThe solvent was distilled off
  5. customthe residue was purified by neutral silica gel column chromatography (chloroform/methanol)

Sources & evidence

ORD record
ord-61ca3607515b440c90ac4cb2ff777b5a
Source dataset
uspto-grants-2014_12
Patent number
US08912181B2

Reaction notes

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