Acetic Acid → HCID 178517960, compound

HRID 1774110Notes

Reaction equation

HRID 1774110 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]=[CH:7][N:6]=[C:5]2[OH:12].[F:13][C:14]1[CH:19]=[CH:18][C:17](B(O)O)=[CH:16][CH:15]=1.C([O-])([O-])=O.[K+].[K+].C(O)(=O)C>O1CCOCC1.O.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>[F:13][C:14]1[CH:19]=[CH:18][C:17]([C:2]2[CH:3]=[C:4]3[C:9](=[CH:10][CH:11]=2)[N:8]=[CH:7][N:6]=[C:5]3[OH:12])=[CH:16][CH:15]=1

Participants

8

Reactant 4

HCID 176Acetic AcidHCID 11430Potassium CarbonateHCID 2856454-Fluorophenylboronic acidHCID 178517953HCID 178517953, compound

Product 1

HCID 178517960HCID 178517960, compoundYield 95%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Procedure

A mixture of 6-bromo-4-hydroxy-quinazoline (2.4 g, 10 mmol), 4-fluorophenylboronic acid (1.54 g, 11 mmol), K2CO3 (4.15 g, 30 mmol) and tetrakis(triphenylphosphine)palladium(0) (0.5 g, 0.43 mmol) in dioxane (150 ml) and water (50 ml) was heated under reflux for 12 hours. After cooling to room temperature, the reaction mixture was neutralized with acetic acid to pH 6-7. The precipitate was collected by filtration, washed with water and diethyl ether to yield the crude product. The crude residue was purified by silica gel flash chromatography, the mobile phase being a mixture of methanol and dichloromethane (in a ratio of 1:40), yielding the pure title compound as a white solid (2.15 g, yield: 95%) which was characterized by its mass spectrum as follows: MS (m/z): 241 ([M+H]+, 100).

Workup

  1. temperaturewas heated
  2. temperatureunder reflux for 12 hours
  3. filtrationThe precipitate was collected by filtration
  4. washwashed with water and diethyl ether
  5. customto yield the crude product
  6. customThe crude residue was purified by silica gel flash chromatography
  7. additiona mixture of methanol and dichloromethane (in a ratio of 1:40),

Sources & evidence

ORD record
ord-a7cde6227e284cc58666c5dc5fcd7daf
Source dataset
uspto-grants-2016_02
Patent number
US09259426B2

Reaction notes

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