Potassium Carbonate → HCID 68352460, compound

HRID 2281133Notes

Reaction equation

HRID 2281133 reaction equation
Br[C:2]1[CH:3]=[N:4][C:5]2[C:10]([CH:11]=1)=[CH:9][CH:8]=[C:7]([F:12])[CH:6]=2.[C:13]([O-])([O-])=O.[K+].[K+].CB1OB(C)OB(C)O1>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.O1CCOCC1>[F:12][C:7]1[CH:6]=[C:5]2[C:10]([CH:11]=[C:2]([CH3:13])[CH:3]=[N:4]2)=[CH:9][CH:8]=1

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 574072TrimethylboroxineHCID 712393083-Bromo-7-fluoroquinoline2×

Product 1

HCID 68352460HCID 68352460, compoundYield 74%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
90 °C

Procedure

3-bromo-7-fluoro-quinoline (Intermediate 30) (100 mg, 0.442 mmol) was combined with K2CO3 (153 mg, 1.10 mmol), anhydrous 1,4-dioxane (3 mL), and trimethylboroxine (0.092 mL, 0.663 mmol). Nitrogen was bubbled in to degas the reaction and Pd(PPh3)4 (50.9 mg, 0.044 mmol) was added. This was degassed again and then heated to 90° C. for 5 h. The reaction was cooled and partitioned between ethyl acetate and sat. aq. NaHCO3. The separated aqueous layer was extracted with ethyl acetate and the combined organics dried over MgSO4. Purification by silica gel flash chromatography (ethyl acetate/heptane) gave 7-fluoro-3-methyl-quinoline (52.7 mg) as a yellow solid. 1H NMR (400 MHz, CDCl3) δ 8.78 (d, J=1.8 Hz, 1 H) 7.93 (s, 1 H) 7.65-7.79 (m, 2 H) 7.32 (td, J=8.6, 2.5 Hz, 1 H) 2.52 (s, 3 H); MS (M+1): 162.1.

Workup

  1. customNitrogen was bubbled in
  2. customto degas
  3. additionwas added
  4. customThis was degassed again
  5. temperatureThe reaction was cooled
  6. custompartitioned between ethyl acetate and sat. aq. NaHCO3
  7. extractionThe separated aqueous layer was extracted with ethyl acetate
  8. dry with materialthe combined organics dried over MgSO4
  9. customPurification by silica gel flash chromatography (ethyl acetate/heptane)

Sources & evidence

ORD record
ord-88ec02742e5c40c39a08d01122ceab63
Source dataset
uspto-grants-2015_09
Patent number
US09139538B2

Reaction notes

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