Toluene → HCID 118113115, compound

HRID 1485061Notes

Reaction equation

HRID 1485061 reaction equation
Br[C:2]1[CH:16]=[CH:15][C:5]([O:6][C:7]2[N:12]=[CH:11][C:10]([CH:13]=[O:14])=[CH:9][CH:8]=2)=[CH:4][CH:3]=1.[CH:17]1(B2OC(C)(C)C(C)(C)O2)[CH2:19][CH2:18]1.C(=O)([O-])[O-].[Cs+].[Cs+].C1(C)C=CC=CC=1>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.O>[CH:17]1([C:2]2[CH:16]=[CH:15][C:5]([O:6][C:7]3[N:12]=[CH:11][C:10]([CH:13]=[O:14])=[CH:9][CH:8]=3)=[CH:4][CH:3]=2)[CH2:19][CH2:18]1

Participants

7

Reactant 4

HCID 1140TolueneHCID 10796Cesium carbonateHCID 27580152-Cyclopropyl-4,4,5,5-tetramethyl-1,3,2-dioxaborolaneHCID 80632509HCID 80632509, compound

Product 1

HCID 118113115HCID 118113115, compoundYield 22.2%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of the compound (3.22 g) obtained in step (1) above, 2-cyclopropyl-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (3.89 g), tetrakis(triphenylphosphine)palladium(0) (669 mg), cesium carbonate (11.3 g), toluene (20.0 mL) and water (10.0 mL) was stirred at 100° C. for 6 hours. After cooling the reaction mixture to room temperature, the precipitate was removed by filtration through Celite (registered trademark). To the filtrate, water and ethyl acetate were added and extraction was conducted with ethyl acetate. The combined organic layers were washed with water and saturated brine successively and after passage through a phase separator, they were concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (n-hexane:ethyl acetate=100:0-50:50) and further purified by preparative HPLC. A saturated aqueous solution of sodium hydrogencarbonate was then added and extraction was conducted with ethyl acetate. The combined organic layers were passed through a phase separator and thereafter concentrated under reduced pressure to give the titled compound as a colorless oil (614 mg).

Workup

  1. temperatureAfter cooling the reaction mixture to room temperature
  2. customthe precipitate was removed by filtration through Celite (registered trademark)
  3. additionTo the filtrate, water and ethyl acetate were added
  4. extractionextraction
  5. washThe combined organic layers were washed with water and saturated brine successively
  6. concentrationafter passage through a phase separator, they were concentrated under reduced pressure
  7. customThe resulting residue was purified by silica gel column chromatography (n-hexane:ethyl acetate=100:0-50:50)
  8. customfurther purified by preparative HPLC
  9. additionA saturated aqueous solution of sodium hydrogencarbonate was then added
  10. extractionextraction
  11. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-daf071ab19754908851db2c4e3124ecc
Source dataset
uspto-grants-2016_08
Patent number
US09422240B2

Reaction notes

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