Sodium Carbonate → 2-Bromo-5-(4-fluorophenyl)pyrazine

HRID 1777435Notes

Reaction equation

HRID 1777435 reaction equation
Br[C:2]1[CH:7]=[N:6][C:5]([Br:8])=[CH:4][N:3]=1.[F:9][C:10]1[CH:15]=[CH:14][C:13](B(O)O)=[CH:12][CH:11]=1.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>[Br:8][C:5]1[CH:4]=[N:3][C:2]([C:13]2[CH:14]=[CH:15][C:10]([F:9])=[CH:11][CH:12]=2)=[CH:7][N:6]=1

Participants

7

Reactant 3

HCID 10340Sodium CarbonateHCID 2856454-Fluorophenylboronic acidHCID 114704212,5-dibromopyrazine

Product 1

HCID 231205542-Bromo-5-(4-fluorophenyl)pyrazineYield 118.5%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 702EthanolSolventHCID 1140TolueneSolvent

Conditions

Temperature
40 °C

Procedure

To a solution of 2,5-dibromopyrazine (100 mg, 0.4 mmol) in toluene (6 mL) and ethanol (3 mL) was added (4-fluorophenyl)boronic acid (29 mg, 0.2 mmol) and 2M sodium carbonate solution (2.84 mL). The solution was purged with argon for 15 min, Pd(PPh3)4 (4 mg, 0.004 mmol) was added, and the reaction mixture was purged with argon for 15 min. The resulting mixture was heated to 40° C. and stirred for 1 h. The reaction mixture was concentrated, diluted with water (20 mL), and extracted with ethyl acetate (2×100 mL). The combined extracts were washed with brine solution (10 mL), and dried over Na2SO4 and concentration in vacuo. The crude product was purified by flash chromatography (60-120μ, 5% ethyl acetate in hexane) to afford 2-bromo-5-(4-fluorophenyl)pyrazine as off-white solid (60 mg, 57% yield). 1H NMR (400 MHz, DMSO-d6): δ 9.08 (s, 1H), 8.88 (s, 1H), 8.18-8.15 (m, 2H), 7.37 (dd, 2H); LC-MS m/z calculated for [M+H]+ 252.97. found 253.0.

Workup

  1. customThe solution was purged with argon for 15 min
  2. customthe reaction mixture was purged with argon for 15 min
  3. concentrationThe reaction mixture was concentrated
  4. additiondiluted with water (20 mL)
  5. extractionextracted with ethyl acetate (2×100 mL)
  6. washThe combined extracts were washed with brine solution (10 mL)
  7. dry with materialdried over Na2SO4 and concentration in vacuo
  8. customThe crude product was purified by flash chromatography (60-120μ, 5% ethyl acetate in hexane)

Sources & evidence

ORD record
ord-6d145671d57a45128c82d63718cd6f3d
Source dataset
uspto-grants-2016_02
Patent number
US09266873B2

Reaction notes

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