Sodium Bicarbonate → 4-(2-Bromo-5-(trifluoromethyl)phenyl)pyridine

HRID 1473283Notes

Reaction equation

HRID 1473283 reaction equation
[Br:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]([F:11])([F:10])[F:9])=[CH:4][C:3]=1I.[N:13]1[CH:18]=[CH:17][C:16](B(O)O)=[CH:15][CH:14]=1.C(=O)(O)[O-].[Na+]>C(COC)OC.O.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[Br:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]([F:11])([F:10])[F:9])=[CH:4][C:3]=1[C:16]1[CH:17]=[CH:18][N:13]=[CH:14][CH:15]=1

Participants

7

Reactant 3

HCID 516892Sodium BicarbonateHCID 2734379(Pyridin-4-yl)boronic acidHCID 467352311-Bromo-2-iodo-4-(trifluoromethyl)benzene

Product 1

HCID 866873404-(2-Bromo-5-(trifluoromethyl)phenyl)pyridineYield 78.1%

Reagents, catalysts & solvents 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 962WaterSolvent2×HCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
90 °C

Procedure

To a solution of compound 1-bromo-2-iodo-4-(trifluoromethyl)benzene (10 g, 28.4 mmol) and pyridin-4-ylboronic acid (7 g, 34.1 mmol) in dimethoxyethane (150 mL) and water (50 mL), sodium bicarbonate (9.54 g, 113.6 mmol) was added. The reaction mixture was purged with nitrogen for 15 minutes and Pd(dppf)2Cl2 (2.3 g, 2.84 mmol) was added. The reaction was stirred at 90° C. for 5 h. Then the reaction mixture was diluted with water (500 mL) extracted with ethyl acetate (2×200 mL). Organic layer was combined, dried over sodium sulfate, filtered and concentrated under a vacuum to give the compound which was further purified by column chromatography using silica gel (100 to 200 mesh) and 0% to 30% ethyl acetate/hexane as eluent to obtain 4-(2-bromo-5-(trifluoromethyl)phenyl)pyridine (6.7 g, 77.6%) as an off white solid. MS (ESI, positive ion) [M+1]+: 301.98; 1H NMR (400 MHz, DMSO) δ 8.71 (d, J=5.9 Hz, 2H), 8.05 (d, J=8.2 Hz, 1H), 7.84-7.75 (d, J=11.3 Hz, 2H), 7.50 (d, J=5.9 Hz, 2H).

Workup

  1. customThe reaction mixture was purged with nitrogen for 15 minutes
  2. extractionextracted with ethyl acetate (2×200 mL)
  3. dry with materialdried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated under a vacuum
  6. customto give the compound which
  7. customwas further purified by column chromatography

Sources & evidence

ORD record
ord-c4bcd6d19ae349d38962e761331b28b6
Source dataset
uspto-grants-2015_04
Patent number
US09012443B2

Reaction notes

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