Sodium hydride → Bis(1,1-dimethylethyl) {3-[(3-bromo-5-chlorophenyl)oxy]-2-fluoro-4-nitrophenyl}propanedioate

HRID 1874932Notes

Reaction equation

HRID 1874932 reaction equation
[H-].[Na+].[C:3]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])(=[O:12])[CH2:4][C:5]([O:7][C:8]([CH3:11])([CH3:10])[CH3:9])=[O:6].[Br:18][C:19]1[CH:20]=[C:21]([O:26][C:27]2[C:32]([F:33])=[C:31](F)[CH:30]=[CH:29][C:28]=2[N+:35]([O-:37])=[O:36])[CH:22]=[C:23]([Cl:25])[CH:24]=1.OS([O-])(=O)=O.[Na+]>C1COCC1>[Br:18][C:19]1[CH:20]=[C:21]([O:26][C:27]2[C:32]([F:33])=[C:31]([CH:4]([C:5]([O:7][C:8]([CH3:9])([CH3:10])[CH3:11])=[O:6])[C:3]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])[CH:30]=[CH:29][C:28]=2[N+:35]([O-:37])=[O:36])[CH:22]=[C:23]([Cl:25])[CH:24]=1

Participants

6

Reactant 4

HCID 24758Sodium hydrideHCID 68324Di-tert-butyl malonateHCID 516919Sodium BisulfateHCID 684866412-[(3-Bromo-5-chlorophenyl)oxy]-3,4-difluoro-1-nitrobenzene

Product 1

HCID 68487247Bis(1,1-dimethylethyl) {3-[(3-bromo-5-chlorophenyl)oxy]-2-fluoro-4-nitrophenyl}propanedioate

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
0 °C

Procedure

Sodium hydride (60% dispersion in oil, 3.95 g, 98.6 mmol) was added to anhydrous THF (100 mL) and cooled to 0° C. under nitrogen. A solution of di-tert-butyl malonate (9.79 g, 45.3 mmol) in THF (20 mL) was added dropwise and the reaction mixture was stirred 30 min. A solution of 2-[(3-bromo-5-chlorophenyl)oxy]-3,4-difluoro-1-nitrobenzene (15.0 g, 41.1 mmol) was added dropwise in THF (50 mL) was added dropwise, the reaction was allowed to warm to RT and stirred for 90 min. The reaction was cooled to 0° C., a solution of saturated aqueous NaHSO4 (200 mL) was added and the aqueous mixture was extracted with EtOAc (3×100 mL). The organic extracts were combined, dried over Na2SO4, filtered and evaporated to afford the title compound a brown solid. 1H NMR (400 MHz, DMSO-d6): δ ppm 8.05 (d, 1H), 7.58 (d, 1H), 7.48 (s, 1H), 7.20 (s, 1H), 7.12 (s, 1H), 3.82-3.80 (m, 1H), 1.35 (s, 18H).

Workup

  1. additionwas added dropwise
  2. temperatureto warm to RT
  3. stirringstirred for 90 min
  4. temperatureThe reaction was cooled to 0° C.
  5. extractionthe aqueous mixture was extracted with EtOAc (3×100 mL)
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. customevaporated

Sources & evidence

ORD record
ord-a40882cfe4ac4839aff1536e5ce2b5bf
Source dataset
uspto-grants-2012_11
Patent number
US08304419B2

Reaction notes

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