Sodium hydride → HCID 11352784, compound

HRID 1831955Notes

Reaction equation

HRID 1831955 reaction equation
[Br:1][C:2]1[C:3](=[O:19])[NH:4][C:5]([CH3:18])=[CH:6][C:7]=1[O:8][CH2:9][C:10]1[CH:15]=[CH:14][C:13]([F:16])=[CH:12][C:11]=1[F:17].[Br:20][CH2:21][C:22]1[CH:27]=[CH:26][CH:25]=[C:24]([CH2:28]Br)[CH:23]=1.[H-].[Na+]>O1CCOCC1>[Br:1][C:2]1[C:3](=[O:19])[N:4]([CH2:28][C:24]2[CH:25]=[CH:26][CH:27]=[C:22]([CH2:21][Br:20])[CH:23]=2)[C:5]([CH3:18])=[CH:6][C:7]=1[O:8][CH2:9][C:10]1[CH:15]=[CH:14][C:13]([F:16])=[CH:12][C:11]=1[F:17]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 69373Benzene, 1,3-bis(bromomethyl)-HCID 220504293-bromo-4-[(2,4-difluorobenzyl)oxy]-6-methylpyridin-2(1H)-one

Product 1

HCID 11352784HCID 11352784, compoundYield 38.6%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
60 °C

Procedure

3-bromo-4-[(2,4-difluorobenzyl)oxy]-6-methylpyridin-2(1H)-one (2 g, 6.06 mmol) was suspended in 1,4-dioxane (250 mL). α,α′-Dibromo-m-xylene (8 g, 30.3 mmol) was added followed by sodium hydride (0.3 g, 7.5 mmol, 60% in mineral oil). The reaction was heated to 60° C. and stirred for 16 hours. The reaction was filtered through Celite® and the filtrate was concentrated to an oil that was partitioned between water and dichloromethane and extracted with dichloromethane (4×250 mL). The organic extracts were combined, washed with brine, dried over Na2SO4, and filtered. The filtrate was concentrated to an oil, and purified by chromatography (silica gel, hexane/ethyl acetate) to yield a white solid (1.2 g, 38%). 1H NMR (400 MHz, CDCl3) δ 7.57 (app q, J=7.6 Hz, 1H); 7.28-7.25 (m, 2H); 7.17 (s, 1H); 7.08 (m, 1H); 6.94 (app dt, J=1.2, 9.6 Hz, 1H), 6.87-6.82 (m, 1H); 5.99 (s, 1H), 5.34 (s, 2H), 5.20 (s, 2H); 4.43 (s, 2H); 2.29 (s, 3H). ES HRMS m/z 511.9672 (M+H C21H17Br2F2NO2 requires 511.9667).

Workup

  1. filtrationThe reaction was filtered through Celite®
  2. concentrationthe filtrate was concentrated to an oil that
  3. customwas partitioned between water and dichloromethane
  4. extractionextracted with dichloromethane (4×250 mL)
  5. washwashed with brine
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. concentrationThe filtrate was concentrated to an oil
  9. custompurified by chromatography (silica gel, hexane/ethyl acetate)

Sources & evidence

ORD record
ord-eb88ab64affc4f7dbca980dde6f4f0d1
Source dataset
uspto-grants-2006_06
Patent number
US07067540B2

Reaction notes

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