Ethanol → 5-Bromo-2-{3-fluoro-4-[(phenylmethyl)oxy]phenyl}pyridine

HRID 423573Notes

Reaction equation

HRID 423573 reaction equation
[CH2:1]([O:8][C:9]1[CH:14]=[CH:13][C:12](B(O)O)=[CH:11][C:10]=1[F:18])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Br[C:20]1[CH:25]=[CH:24][C:23]([Br:26])=[CH:22][N:21]=1.C([O-])([O-])=O.[Na+].[Na+].CCO>C1(C)C=CC=CC=1.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:26][C:23]1[CH:24]=[CH:25][C:20]([C:12]2[CH:13]=[CH:14][C:9]([O:8][CH2:1][C:2]3[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=3)=[C:10]([F:18])[CH:11]=2)=[N:21][CH:22]=1

Participants

7

Reactant 4

HCID 702EthanolHCID 10340Sodium CarbonateHCID 693532,5-DibromopyridineHCID 27377884-Benzyloxy-3-fluorophenylboronic Acid

Product 1

HCID 666732465-Bromo-2-{3-fluoro-4-[(phenylmethyl)oxy]phenyl}pyridineYield 77%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 1140TolueneSolvent

Conditions

Temperature
90 °C

Procedure

(4-Benzyloxy-3-fluorophenyl)boronic acid (1.06 g, 4.22 mmol) was added to a suspension of 2,5-dibromopyridine (1.0 g, 4.22 mmol) in toluene (8 mL), followed by addition of 2M Na2CO3 (6 mL) and Pd(PPh3)4 (0.15 g, 0.13 mmol) and EtOH (2 mL). The reaction mixture was degassed with N2 and heated at 90° C. overnight. The mixture was cooled to ambient temperature, water was added, and the mixture was extracted with EtOAc. The combined organic extract was washed with brine, dried over Na2SO4, filtered through a pad of silica gel, and the filtrate was concentrated to give a solid, which was recrystallized from MeOH to give 1.16 g (77%) of 5-bromo-2-{3-fluoro-4-[(phenylmethyl)oxy]phenyl}pyridine as a faint yellow solid. 1H NMR (400 MHz, CDCl3): δ 8.69 (d, 1H, J=2.2 Hz), 7.85 (dd, 1H, Ja=8.4 Hz, Jb=2.1 Hz), 7.77 (dd, 1H, Ja=12.4 Hz, Jb=2.1 Hz), 7.67 (d, 1H, J=8.6 Hz), 7.54 (d, 1H, J=8.5 Hz), 7.50-7.30 (m, 5H), 7.07 (t, 1H, J=8.4 Hz), 5.20 (s, 2H); LRMS (ESI), m/z 358/360 (M+H).

Workup

  1. customThe reaction mixture was degassed with N2
  2. temperatureThe mixture was cooled to ambient temperature
  3. additionwater was added
  4. extractionthe mixture was extracted with EtOAc
  5. extractionThe combined organic extract
  6. washwas washed with brine
  7. dry with materialdried over Na2SO4
  8. filtrationfiltered through a pad of silica gel
  9. concentrationthe filtrate was concentrated
  10. customto give a solid, which
  11. customwas recrystallized from MeOH

Sources & evidence

ORD record
ord-d9dcb8ef6a5f4ae3b5f6bb92c8556051
Source dataset
uspto-grants-2012_01
Patent number
US08101634B2

Reaction notes

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