Water → 2-Fluoro-3-(pyrimidin-5-yl)benzonitrile

HRID 593744Notes

Reaction equation

HRID 593744 reaction equation
Br[C:2]1[CH:3]=[N:4][CH:5]=[N:6][CH:7]=1.C(=O)([O-])[O-].[Na+].[Na+].[C:14]([C:16]1[C:17]([F:25])=[C:18](B(O)O)[CH:19]=[CH:20][CH:21]=1)#[N:15].O>COCCOC.[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.CCO>[F:25][C:17]1[C:18]([C:2]2[CH:3]=[N:4][CH:5]=[N:6][CH:7]=2)=[CH:19][CH:20]=[CH:21][C:16]=1[C:14]#[N:15]

Participants

8

Reactant 4

HCID 962WaterHCID 10340Sodium CarbonateHCID 783445-BromopyrimidineHCID 445581733-Cyano-2-fluorobenzeneboronic acid

Product 1

HCID 867304012-Fluoro-3-(pyrimidin-5-yl)benzonitrileYield 24%

Reagents, catalysts & solvents 3

HCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 702EthanolSolventHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
70 °C

Procedure

A sealed tube apparatus was charged with a solution containing 5-bromopyrimidine (1 g, 6.29 mmol), sodium carbonate (3.33 g, 31.4 mmol), and 3-cyano-2-fluorophenylboronic acid (1.037 g, 6.29 mmol) in a mixture of DME (Ratio: 2, Volume: 31.4 ml), water (Ratio: 1.000, Volume: 15.72 ml), and EtOH (Ratio: 1.000, Volume: 15.72 ml) at ambient temperature. Tetrakis(triphenylphosphine) palladium(0) (0.363 g, 0.314 mmol) was then added and the system was purged with nitrogen, sealed, and heated to 70° C. for 12 h. The vessel was cooled to room temperature and diluted with EtOAc and water. The mixture was further diluted with brine and extracted three times with EtOAc. The combined organics were dried over MgSO4, filtered, and concentrated to give the crude product. The crude material was purified by flash chromatography on silica using an ISCO machine (40 g SiO2 column, 40 mL/min, 0-40% EtOAc/hexanes over 15 minutes, tr=8 minutes) to afford the title compound (300 mg, 24%). ESI MS (M+H)+=200.0. 1H NMR (400 MHz, DMSO-d6) δ ppm 9.28 (1 hr, s), 9.09 (2 hr, d, J=1.54 Hz), 8.02-8.12 (2 hr, m), 7.59 (1 hr, t, J=7.81 Hz).

Workup

  1. additionA sealed tube apparatus was charged with a solution
  2. customthe system was purged with nitrogen
  3. customsealed
  4. temperatureThe vessel was cooled to room temperature
  5. additiondiluted with EtOAc and water
  6. additionThe mixture was further diluted with brine
  7. extractionextracted three times with EtOAc
  8. dry with materialThe combined organics were dried over MgSO4
  9. filtrationfiltered
  10. concentrationconcentrated
  11. customto give the crude product
  12. customThe crude material was purified by flash chromatography on silica using an ISCO machine (40 g SiO2 column, 40 mL/min, 0-40% EtOAc/hexanes over 15 minutes, tr=8 minutes)

Sources & evidence

ORD record
ord-5a48945e6959421a96cd45257759adca
Source dataset
uspto-grants-2016_01
Patent number
US09242967B2

Reaction notes

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