Potassium Phosphate, Tribasic → HCID 68487701, compound

HRID 1191558Notes

Reaction equation

HRID 1191558 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[C:45]([F:48])([F:47])[F:46].Br[C:50]1[CH:51]=[CH:52][C:53]([CH2:68][CH3:69])=[C:54]([CH:56]2[C:61](=[O:62])[C:60]([CH3:64])([CH3:63])[O:59][C:58]([CH3:66])([CH3:65])[C:57]2=[O:67])[CH:55]=1.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>CN(C)C=O.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:50]2[CH:51]=[CH:52][C:53]([CH2:68][CH3:69])=[C:54]([CH:56]3[C:61](=[O:62])[C:60]([CH3:64])([CH3:63])[O:59][C:58]([CH3:66])([CH3:65])[C:57]3=[O:67])[CH:55]=2)=[CH:38][C:37]=1[C:45]([F:48])([F:47])[F:46]

Participants

8

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 27826714-Chloro-3-(trifluoromethyl)benzeneboronic acidHCID 666785694-(5-Bromo-2-ethylphenyl)-2,2,6,6-tetramethylpyran-3,5-dioneHCID 86657037CID 86657037

Product 1

HCID 68487701HCID 68487701, compoundYield 53.5%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 6228DimethylformamideSolventHCID 6342AcetonitrileSolvent

Conditions

Temperature
160 °C

Procedure

To a microwave vial is added palladium(II) acetate (3.3 mg, 0.015 mmol), tris(3-sulfophenyl)phosphine trisodium salt (22 mg, 0.038 mmol), 4-chloro-3-trifluoromethylphenyl boronic acid (0.200 g, 0.89 mmol), 4-(5-bromo-2-ethylphenyl)-2,2,6,6-tetramethylpyran-3,5-dione (0.208 g, 0.59 mmol) and potassium phosphate (0.625 g, 2.95 mmol). A degassed mixed solution of acetonitrile/distilled water (1.5 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 argon. 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 ethyl acetate (3 ml) and acidified to pH2 with dilute aqueous hydrochloric acid. The organic phase is separated and the aqueous phase is further extracted with ethyl acetate (2×3 ml). All organics are then combined, filtered through a silica plug and evaporated to give a crude product which is dissolved in N,N-dimethylformamide (2.5 ml) and purified by preparative reverse phase HPLC to afford 4-(4′-chloro-4-ethyl-3′-trifluoromethylbiphenyl-3-yl)-2,2,6,6-tetramethylpyran-3,5-dione (0.143 g) as a white powder.

Workup

  1. distillationdistilled water (1.5 ml, 1:1 ratio)
  2. additionis next added (
  3. washwashing-down any solids from the slides of the vial),
  4. customflushing with argon
  5. temperatureAfter cooling to room temperature the reaction mixture
  6. additionis diluted with ethyl acetate (3 ml)
  7. customThe organic phase is separated
  8. extractionthe aqueous phase is further extracted with ethyl acetate (2×3 ml)
  9. filtrationfiltered through a silica plug
  10. customevaporated
  11. customto give a crude product which
  12. custompurified by preparative reverse phase HPLC

Sources & evidence

ORD record
ord-e2daa8123b32425eb52f5c2aac8f65b7
Source dataset
uspto-grants-2014_03
Patent number
US08680012B2

Reaction notes

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