4-(Ethylsulphonyl)benzeneboronic acid → 2-(4'-Ethylsulfonyl-6-fluorobiphenyl-3-yl)-2,3-dihydro-1H-1,3-diaza-2-boraphenalene

HRID 1846039Notes

Reaction equation

HRID 1846039 reaction equation
[CH2:1]([S:3]([C:6]1[CH:11]=[CH:10][C:9](B(O)O)=[CH:8][CH:7]=1)(=[O:5])=[O:4])[CH3:2].Cl[C:16]1[CH:17]=[C:18]([B:23]2[NH:34][C:33]3[C:35]4[C:29]([CH:30]=[CH:31][CH:32]=3)=[CH:28][CH:27]=[CH:26][C:25]=4[NH:24]2)[CH:19]=[CH:20][C:21]=1[F:22].P([O-])([O-])[O-].[K+].[K+].[K+].C1(P(C2CCCCC2)C2C=CC=CC=2C2C(OC)=CC=CC=2OC)CCCCC1>CN(C=O)C>[CH2:1]([S:3]([C:6]1[CH:11]=[CH:10][C:9]([C:16]2[C:21]([F:22])=[CH:20][CH:19]=[C:18]([B:23]3[NH:24][C:25]4[C:35]5[C:29]([CH:28]=[CH:27][CH:26]=4)=[CH:30][CH:31]=[CH:32][C:33]=5[NH:34]3)[CH:17]=2)=[CH:8][CH:7]=1)(=[O:5])=[O:4])[CH3:2]

Participants

6

Reactant 4

HCID 27734204-(Ethylsulphonyl)benzeneboronic acidHCID 9837043phosphorous acid, tripotassium saltHCID 112698722-Dicyclohexylphosphino-2',6'-dimethoxybiphenylHCID 867232622-(3-Chloro-4-fluorophenyl)-2,3-dihydro-1H-naphtho[1,8-de][1,3,2]diazaborinine

Product 1

HCID 867232612-(4'-Ethylsulfonyl-6-fluorobiphenyl-3-yl)-2,3-dihydro-1H-1,3-diaza-2-boraphenaleneYield 42%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a room temperature solution of 4-(ethylsulphonyl)benzeneboronic acid (0.90 g, 4.22 mmol) in anhydrous DMF (20 mL) was added 2-(3-chloro-4-fluorophenyl)-2,3-dihydro-1H-1,3-diaza-2-boraphenalene (Preparation 81, 1.00 g, 3.37 mmol) and potassium phosphite (2.87 g, 13.5 mmol) and the reaction mixture was degassed with argon for 30 minutes. To this was added 2-dicyclohexylphosphino-2′,6′-dimethoxybiphenyl (276.7 mg, 0.67 mmol) followed by the tris(dibenzilideneacetone)palladium(0) (154 mg, 0.168 mmol) and the resultant solution was heated to 100° C. with stirring for 12 hours. The reaction mixture was cooled then filtered through a pad of celite. The pad was rinsed well with EtOAc (100 mL) and the filtrate was washed with water (2×50 mL) then saturated brine solution and dried over anhydrous MgSO4 (s), filtered and evaporated in vacuo to give crude product as a yellow oil. The residue was purified by silica gel column chromatography eluting with CH2Cl2:MeOH 98:2 to afford the title compound as a colourless oil in 42% yield, 600 mg.

Workup

  1. customthe reaction mixture was degassed with argon for 30 minutes
  2. temperatureThe reaction mixture was cooled
  3. filtrationthen filtered through a pad of celite
  4. washThe pad was rinsed well with EtOAc (100 mL)
  5. washthe filtrate was washed with water (2×50 mL)
  6. dry with materialsaturated brine solution and dried over anhydrous MgSO4 (s)
  7. filtrationfiltered
  8. customevaporated in vacuo
  9. customto give crude product as a yellow oil
  10. customThe residue was purified by silica gel column chromatography
  11. washeluting with CH2Cl2:MeOH 98:2

Sources & evidence

ORD record
ord-edddb4cc214d4efba859479a9906a855
Source dataset
uspto-grants-2015_02
Patent number
US08952008B2

Reaction notes

Loading…