Hydrochloric Acid → Bis(1,1-dimethylethyl)(3-{[3-cyano-5-(methyloxy)phenyl]oxy}-2-fluoro-4-nitrophenyl)propanedioate

HRID 1875241Notes

Reaction equation

HRID 1875241 reaction equation
[C:1]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])(=[O:10])[CH2:2][C:3]([O:5][C:6]([CH3:9])([CH3:8])[CH3:7])=[O:4].[H-].[Na+].[F:18][C:19]1[C:24](F)=[CH:23][CH:22]=[C:21]([N+:26]([O-:28])=[O:27])[C:20]=1[O:29][C:30]1[CH:31]=[C:32]([CH:35]=[C:36]([O:38][CH3:39])[CH:37]=1)[C:33]#[N:34].Cl>C1COCC1>[CH3:13][C:12]([O:11][C:1](=[O:10])[CH:2]([C:24]1[CH:23]=[CH:22][C:21]([N+:26]([O-:28])=[O:27])=[C:20]([O:29][C:30]2[CH:37]=[C:36]([O:38][CH3:39])[CH:35]=[C:32]([C:33]#[N:34])[CH:31]=2)[C:19]=1[F:18])[C:3]([O:5][C:6]([CH3:7])([CH3:8])[CH3:9])=[O:4])([CH3:15])[CH3:14]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 24758Sodium hydrideHCID 68324Di-tert-butyl malonateHCID 687222673-[(2,3-Difluoro-6-nitrophenyl)oxy]-5-(methyloxy)benzonitrile

Product 1

HCID 68724212Bis(1,1-dimethylethyl)(3-{[3-cyano-5-(methyloxy)phenyl]oxy}-2-fluoro-4-nitrophenyl)propanedioateYield 97%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

Di-tert-butyl malonate (11.22 g, 51.9 mmol) was added dropwise. to a 0° C. solution of NaH (5.09 g, 127 mmol) in THF (150 ml). The reaction mixture was allowed to warm to RT, stirred for an additional 30 mins, and cooled to 0° C. A solution of 3-[(2,3-difluoro-6-nitrophenyl)oxy]-5-(methyloxy)benzonitrile (14.44 g, 47.2 mmol) in THF (50 mL) was added slowly and the reaction mixture was stirred at RT overnight. Dilute HCl was carefully added and the solution was extracted with EtOAc (3×100 mL). The organic layer was dried (Na2SO4), filtered, concentrated, and purified by silica gel chromatography (0-35% EtOAc/hexanes) to afford the title compound (22.9 g, 97%) as a light yellow solid. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 7.88 (dd, J=8.79, 1.46 Hz, 1H) 7.62 (dd, J=8.65, 6.46 Hz, 1H) 6.92 (s, 1H) 6.68-6.79 (m, 2 H) 4.81 (s, 1H) 3.83 (s, 3H) 1.49 (s, 16H).

Workup

  1. customto a 0° C.
  2. temperaturecooled to 0° C
  3. stirringthe reaction mixture was stirred at RT overnight
  4. extractionthe solution was extracted with EtOAc (3×100 mL)
  5. dry with materialThe organic layer was dried (Na2SO4)
  6. filtrationfiltered
  7. concentrationconcentrated
  8. custompurified by silica gel chromatography (0-35% EtOAc/hexanes)

Sources & evidence

ORD record
ord-e1e1e71f5a524fc48fa3899fe2e91590
Source dataset
uspto-grants-2012_11
Patent number
US08304419B2

Reaction notes

Loading…