Potassium Phosphate, Tribasic → 3-(4'-Chloro-4-ethyl-3'-methylbiphen-3-yl)bicyclo[3.2.1]octane-2,4-dione

HRID 72264Notes

Reaction equation

HRID 72264 reaction equation
[Na].[Na].[Na].S(C1C=C(P(C2C=CC=C(S(O)(=O)=O)C=2)C2C=CC=C(S(O)(=O)=O)C=2)C=CC=1)(O)(=O)=O.[Cl:35][C:36]1[CH:41]=[CH:40][C:39](B(O)O)=[CH:38][C:37]=1[CH3:45].Br[C:47]1[CH:48]=[CH:49][C:50]([CH2:63][CH3:64])=[C:51]([CH:53]2[C:59](=[O:60])[CH:58]3[CH2:61][CH:55]([CH2:56][CH2:57]3)[C:54]2=[O:62])[CH:52]=1.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C(#N)C>[Cl:35][C:36]1[CH:41]=[CH:40][C:39]([C:47]2[CH:48]=[CH:49][C:50]([CH2:63][CH3:64])=[C:51]([CH:53]3[C:54](=[O:62])[CH:55]4[CH2:61][CH:58]([CH2:57][CH2:56]4)[C:59]3=[O:60])[CH:52]=2)=[CH:38][C:37]=1[CH3:45]

Participants

7

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 3786632(4-Chloro-3-methylphenyl)boronic acidHCID 666795693-(5-Bromo-2-ethylphenyl)bicyclo[3.2.1]octane-2,4-dioneHCID 86657037CID 86657037

Product 1

HCID 907005143-(4'-Chloro-4-ethyl-3'-methylbiphen-3-yl)bicyclo[3.2.1]octane-2,4-dione

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 6342AcetonitrileSolvent

Conditions

Temperature
160 °C

Procedure

To a microwave vial is added palladium(II) acetate (3.7 mg, 0.016 mmol), tris(3-sulfophenyl)phosphine trisodium salt (23 mg, 0.041 mmol), 4-chloro-3-methylphenyl boronic acid (0.167 g, 0.97 mmol), 3-(5-bromo-2-ethyl-phenyl)-bicyclo[3.2.1]octane-2,4-dione (0.209 g, 0.65 mmol) and potassium phosphate (0.691 g, 3.26 mmol). A degassed mixed solution of acetonitrile/distilled water (1.6 ml, 1:1 ratio) is next added (washing-down any solids from the slides of the vial), followed by stirring for 5 minutes and flushing with nitrogen. This mixture is then heated at 160° C. under microwave irradiation for 15 minutes. After cooling to room temperature the reaction mixture is diluted with N,N-dimethylformamide (1 ml), then partitioned between 2M hydrochloric acid and dichloromethane. After the organic phase is separated the aqueous phase is again washed with dichloromethane, then all organic fractions are combined and concentrated in vacuo to afford a crude gum. This crude product is then purified by preparative reverse-phase HPLC to afford 3-(4′-chloro-4-ethyl-3′-methylbiphen-3-yl)bicyclo[3.2.1]octane-2,4-dione.

Workup

  1. distillationdistilled water (1.6 ml, 1:1 ratio)
  2. additionis next added (
  3. washwashing-down any solids from the slides of the vial),
  4. customflushing with nitrogen
  5. temperatureAfter cooling to room temperature the reaction mixture
  6. additionis diluted with N,N-dimethylformamide (1 ml)
  7. custompartitioned between 2M hydrochloric acid and dichloromethane
  8. customAfter the organic phase is separated the aqueous phase
  9. washis again washed with dichloromethane
  10. concentrationconcentrated in vacuo
  11. customto afford a crude gum
  12. customThis crude product is then purified by preparative reverse-phase HPLC

Sources & evidence

ORD record
ord-6159cf7478804a878b72077db32f33cc
Source dataset
uspto-grants-2014_09
Patent number
US08828908B2

Reaction notes

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