Dichloromethane → HCID 178497719, compound

HRID 1487837Notes

Reaction equation

HRID 1487837 reaction equation
[CH3:1][C:2]1[CH:11]=[CH:10][C:5]([C:6]([O:8][CH3:9])=[O:7])=[CH:4][C:3]=1B1OC(C)(C)C(C)(C)O1.I[C:22]1[NH:26][C:25]([CH3:27])=[N:24][C:23]=1[CH3:28].C([O-])([O-])=O.[K+].[K+].C(Cl)Cl>C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[CH3:27][C:25]1[NH:26][C:22]([C:3]2[CH:4]=[C:5]([CH:10]=[CH:11][C:2]=2[CH3:1])[C:6]([O:8][CH3:9])=[O:7])=[C:23]([CH3:28])[N:24]=1

Participants

6

Reactant 4

HCID 6344Dichloromethane2×HCID 11430Potassium Carbonate2×HCID 532171365-Methoxycarbonyl-2-methylphenylboronic acid pinacol ester2×HCID 178432771HCID 178432771, compound2×

Product 1

HCID 178497719HCID 178497719, compoundYield 77%

Reagents, catalysts & solvents 1

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)Catalyst2×

Conditions

Temperature
90 °C

Procedure

Methyl 4-methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzoate (compound 5.4, 3.56 g, 12.9 mmol), 5-iodo-2,4-dimethyl-1H-imidazole (compound 5.5, 3.43 g, 15.4 mmol), K2CO3 (5.33 g, 38.6 mmol) and PdCl2(dppf).CH2Cl2 (1.05 g, 1.29 mmol) were added to a round bottom flask. The flask was purged with argon, then dioxane (70 mL) and water (20 mL) were added and the mixture was heated at 90° C. for 16 hours. The mixture was cooled then additional K2CO3 (1M, 25 mL, 25.0 mmol) and catalyst PdCl2(dppf).CH2Cl2 (1.0 g, 1.2 mmol) were added. The mixture was heated at 90° C. for an additional 10 hours, then cooled to room temperature and filtered through Celite®. The solvent was removed under reduced pressure and the residue was cooled to 0° C. and acidified to pH 3-4 with aqueous HCl (2 M). The acidic mixture was washed with EtOAc (150 mL) and then the aqueous material was adjusted to pH 10-11 with aqueous sodium hydroxide (2 M) and extracted with EtOAc (5×200 mL). The combined organic phases were dried (MgSO4), filtered, and concentrated under reduced pressure. The residue was purified by column chromatography (DCM to 5% MeOH in DCM) to yield the title compound as a thick brown oil (2.42 g, 77%). m/z (ES+) 245(M+H)+. 1H NMR (400 MHz, CDCl3) δ 7.89-7.87 (m, 2H), 7.31 (d with fine str, J=8.6 Hz, 1H), 3.89 (s, 3H), 2.38 (s, 3H), 2.31 (s, 3H), 2.11 (s, 3H).

Workup

  1. customThe flask was purged with argon
  2. additiondioxane (70 mL) and water (20 mL) were added
  3. temperatureThe mixture was cooled
  4. temperatureThe mixture was heated at 90° C. for an additional 10 hours
  5. temperaturecooled to room temperature
  6. filtrationfiltered through Celite®
  7. customThe solvent was removed under reduced pressure
  8. temperaturethe residue was cooled to 0° C.
  9. washThe acidic mixture was washed with EtOAc (150 mL)
  10. extractionextracted with EtOAc (5×200 mL)
  11. dry with materialThe combined organic phases were dried (MgSO4)
  12. filtrationfiltered
  13. concentrationconcentrated under reduced pressure
  14. customThe residue was purified by column chromatography (DCM to 5% MeOH in DCM)

Sources & evidence

ORD record
ord-56703064c75b497580e26a4c39fb751c
Source dataset
uspto-grants-2016_08
Patent number
US09428502B2

Reaction notes

Loading…