Sodium Carbonate → 3-Fluoro-4'-[(4-hydroxyphenyl)(3,3,5,5-tetramethylcyclohexylidene)methyl]-4-biphenylcarbonitrile

HRID 229295Notes

Reaction equation

HRID 229295 reaction equation
CS(C1C=CC(C2C=CC(C(=C3CC(C)(C)CC(C)(C)C3)C3C=CC(O)=CC=3)=CC=2)=CC=1)(=O)=O.Br[C:36]1[CH:41]=[CH:40][C:39]([C:42](=[C:50]2[CH2:55][C:54]([CH3:57])([CH3:56])[CH2:53][C:52]([CH3:59])([CH3:58])[CH2:51]2)[C:43]2[CH:48]=[CH:47][C:46]([OH:49])=[CH:45][CH:44]=2)=[CH:38][CH:37]=1.[C:60]([C:62]1[CH:67]=[CH:66][C:65](B(O)O)=[CH:64][C:63]=1[F:71])#[N:61].C([O-])([O-])=O.[Na+].[Na+]>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.O.C1COCC1>[F:71][C:63]1[CH:64]=[C:65]([C:36]2[CH:41]=[CH:40][C:39]([C:42]([C:43]3[CH:44]=[CH:45][C:46]([OH:49])=[CH:47][CH:48]=3)=[C:50]3[CH2:51][C:52]([CH3:59])([CH3:58])[CH2:53][C:54]([CH3:56])([CH3:57])[CH2:55]3)=[CH:38][CH:37]=2)[CH:66]=[CH:67][C:62]=1[C:60]#[N:61]

Participants

8

Reactant 4

HCID 10340Sodium CarbonateHCID 2783130(4-Cyano-3-fluorophenyl)boronic acidHCID 111557414-[[4'-(Methylsulfonyl)-4-biphenylyl](3,3,5,5-tetramethylcyclohexylidene)methyl]phenolHCID 686543984-[(4-Bromophenyl)(3,3,5,5-tetramethylcyclohexylidene)methyl]phenol

Product 1

HCID 113511513-Fluoro-4'-[(4-hydroxyphenyl)(3,3,5,5-tetramethylcyclohexylidene)methyl]-4-biphenylcarbonitrileYield 72%

Reagents, catalysts & solvents 3

HCID 178418476HCID 178418476, compoundCatalystHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

The Suzuki protocol described for (163) was employed. A round-bottomed flask was charged with 4-[(4-bromophenyl)(3,3,5,5-tetramethylcyclohexylidene)methyl]phenol (14) (0.200 g, 0.5 mmol), PdCl2(PPh3)2 (0.035 g, 0.05 mmol), (4-cyano-3-fluorophenyl)boronic acid (0.165 g, 1.0 mmol), aqueous 2 M Na2CO3 (1.0 mL, 0.106 g, 1.0 mmol) solution, and 4:1 THF:H2O (5 mL) under a nitrogen atmosphere. The reaction mixture was refluxed for 12 h. Regular work-up and purification gave 0.158 g (72%) of the title compound (237) as an off-white solid. 1H NMR (400 MHz, DMSO-d6): δ 9.30 (s, 1H), 7.96 (dd, J1=7.2 Hz, J2=7.2 Hz, 1H), 7.88 and 7.85 (dd, J1=11.2 Hz, J2=1.2 Hz, 1H), 7.73 (d, J=8.4 Hz, 3H), 7.25 (d, J=8.4 Hz, 2H), 7.45 (d, J=8.8 Hz, 2H), 7.17 (d, J=8.4 Hz, 2H), 1.93 (s, 2H), 1.92 (s, 2H), 1.26 (s, 2H), 0.89 (s, 6H), 0.88 (s, 6H). LCMS (APCI): m/z 437.97 (M−H)−.

Workup

  1. temperatureThe reaction mixture was refluxed for 12 h
  2. customRegular work-up and purification

Sources & evidence

ORD record
ord-bf95fbd453b04f9bae099041769b7e02
Source dataset
uspto-grants-2009_07
Patent number
US07560589B2

Reaction notes

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