Potassium Carbonate → HCID 86679888, compound

HRID 1519398Notes

Reaction equation

HRID 1519398 reaction equation
Br[C:2]1[CH:11]=[CH:10][C:9]([C:12]2[S:13][CH:14]=[C:15]([C:17]3[CH:22]=[CH:21][C:20]([Cl:23])=[C:19]([Cl:24])[CH:18]=3)[N:16]=2)=[CH:8][C:3]=1[C:4]([O:6]C)=[O:5].O1CCOCC1.C([O-])([O-])=O.[K+].[K+].[C:37]1(B(O)O)[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=1>C(Cl)Cl.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:24][C:19]1[CH:18]=[C:17]([C:15]2[N:16]=[C:12]([C:9]3[CH:8]=[C:3]([C:4]([OH:6])=[O:5])[C:2]([C:37]4[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=4)=[CH:11][CH:10]=3)[S:13][CH:14]=2)[CH:22]=[CH:21][C:20]=1[Cl:23]

Participants

7

Reactant 4

HCID 11430Potassium CarbonateHCID 312751,4-DioxaneHCID 66827Phenylboronic AcidHCID 86679833Methyl 2-bromo-5-(4-(3,4-dichlorophenyl)thiazol-2-yl)benzoate

Product 1

HCID 86679888HCID 86679888, compoundYield 20%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 6344DichloromethaneSolvent

Conditions

Temperature
100 °C

Procedure

Methyl 2-bromo-5-(4-(3,4-dichlorophenyl)thiazol-2-yl)benzoate (177 mg, 0.4 mmol) was taken up in CH2Cl2 and washed with aqueous Na2CO3. The organic layer was dried (MgSO4), filtered, and evaporated. Dioxane (2 mL) was added, along with tetrakis(triphenylphosphine)palladium(0) (37 mg, 0.032 mmol), 3 M aqueous K2CO3 (267 μL, 0.8 mmol) and phenylboronic acid (available from ASDI Incorporated; 97.5 mg, 0.8 mmol). The vial was evacuated and filled with nitrogen, and then the mixture was heated at 100° C. for 20 h. The mixture was purified on an ISCO Combiflash system, using 0-15% ethyl acetate/hexanes as eluent. Fractions homogeneous for the product were evaporated, and the resulting material was dissolved in THF (2 mL). 1 M aqueous NaOH (2 mL) was added and the mixture was heated at 60° C. overnight. 1 M aqueous HCl was added to bring the pH to approximately 2, and the mixture was extracted 4 times with EtOAc. The combined organic layers were washed with brine, dried (Na2SO4), filtered, evaporated, and purified by preparative HPLC, using the conditions outlined in General Procedure A for Suzuki Coupling and Hydrolysis in Parallel Mode, to give 4-[4-(3,4-dichloro-phenyl)-thiazol-2-yl]-biphenyl-2-carboxylic acid (33 mg, 20%) as a yellow solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 8.45 (s, 1H), 8.32 (d, J=1.6 Hz, 2H), 8.20 (dd, J=8.2, 2.0 Hz, 1H), 8.07 (dd, J=8.2, 2.0 Hz, 1H), 7.74 (d, J=8.6 Hz, 1H), 7.55 (d, J=8.2 Hz, 1H), 7.35-7.48 (m, 5H).

Workup

  1. washwashed with aqueous Na2CO3
  2. dry with materialThe organic layer was dried (MgSO4)
  3. filtrationfiltered
  4. customevaporated
  5. customThe vial was evacuated
  6. additionfilled with nitrogen
  7. customThe mixture was purified on an ISCO Combiflash system
  8. customFractions homogeneous for the product were evaporated
  9. dissolutionthe resulting material was dissolved in THF (2 mL)
  10. addition1 M aqueous NaOH (2 mL) was added
  11. temperaturethe mixture was heated at 60° C. overnight
  12. addition1 M aqueous HCl was added
  13. extractionthe mixture was extracted 4 times with EtOAc
  14. washThe combined organic layers were washed with brine
  15. dry with materialdried (Na2SO4)
  16. filtrationfiltered
  17. customevaporated
  18. custompurified by preparative HPLC
  19. customoutlined in General Procedure A for Suzuki Coupling and Hydrolysis in Parallel Mode

Sources & evidence

ORD record
ord-f736a76feabc450c9c1fcd533dfcc16f
Source dataset
uspto-grants-2015_07
Patent number
US09073881B2

Reaction notes

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