Sodium Carbonate → HCID 86680485, compound

HRID 2406448Notes

Reaction equation

HRID 2406448 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5]([C:8](=[O:10])[CH3:9])=[N:6][CH:7]=1.CC1(C)C(C)(C)OB([C:19]2[CH:20]=[CH:21][C:22]([C:25]#[N:26])=[N:23][CH:24]=2)O1.C([O-])([O-])=O.[Na+].[Na+]>C1(C)C=CC=CC=1.C(O)C.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>[C:8]([C:5]1[N:6]=[CH:7][C:2]([C:19]2[CH:24]=[N:23][C:22]([C:25]#[N:26])=[CH:21][CH:20]=2)=[CH:3][CH:4]=1)(=[O:10])[CH3:9]

Participants

7

Reactant 3

HCID 10340Sodium CarbonateHCID 164141882-Cyanopyridine-5-boronic acid pinacol esterHCID 231453451-(5-Bromopyridin-2-yl)ethan-1-one

Product 1

HCID 86680485HCID 86680485, compoundYield 80.6%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 702EthanolSolventHCID 1140TolueneSolvent

Conditions

Temperature
77.5 °C

Procedure

To a stirred solution of 1-(5-bromopyridin-2-yl)ethanone (0.2 g, 1 mmol) in toluene (10 mL) and ethanol (5 mL) was added 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)picolinonitrile (0.46 g, 2 mmol) and Pd(PPh3)4 (0.057 g, 0.05 mmol). The reaction mixture was purged with argon for 5 min, 2M Na2CO3 solution (3.5 mL, 0.74 g, 7 mmol) was added, and the reaction mixture was stirred at 75-80° C. for 6 h. The reaction mixture was cooled to room temperature, quenched with saturated sodium bicarbonate solution (2×100 mL), and extracted into ethyl acetate (2×100 mL). The organic layer was washed with brine and ice-cold water (2×100 mL), dried over sodium sulfate, filtered and concentrated under reduced pressure to obtain crude product. The crude product was purified by column chromatography (100-200μ silica gel, using 15-16% ethyl acetate in hexane) to obtain 6′-acetyl-[3,3′-bipyridine]-6-carbonitrile as white solid (0.18 g, 80% yield). 1H NMR (400 MHz, DMSO-d6): δ 9.24 (dd, 1H), 9.20 (dd, 1H), 8.54 (dd, 1H), 8.46 (dd, 1H), 8.23 (dd, 1H), 8.09 (dd, 1H), 2.68 (s, 3H); LC-MS m/z calculated for [M+H]+ 224.07, found 224.1.

Workup

  1. customThe reaction mixture was purged with argon for 5 min
  2. temperatureThe reaction mixture was cooled to room temperature
  3. customquenched with saturated sodium bicarbonate solution (2×100 mL)
  4. extractionextracted into ethyl acetate (2×100 mL)
  5. washThe organic layer was washed with brine and ice-cold water (2×100 mL)
  6. dry with materialdried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customto obtain crude product
  10. customThe crude product was purified by column chromatography (100-200μ silica gel, using 15-16% ethyl acetate in hexane)

Sources & evidence

ORD record
ord-6a7231df250e4fb7b5c3b0dbd97c0414
Source dataset
uspto-grants-2014_08
Patent number
US08809372B2

Reaction notes

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