Dimethyl malonate → HCID 117600964, compound

HRID 578954Notes

Reaction equation

HRID 578954 reaction equation
Br[C:2]1[C:9]([CH3:10])=[CH:8][C:5]([C:6]#[N:7])=[C:4]([F:11])[CH:3]=1.C(OC)(=O)[CH2:13][C:14]([O:16][CH3:17])=[O:15].C(=O)([O-])[O-].[K+].[K+].C(=O)([O-])O.[K+]>C(OCC)(=O)C.F[B-](F)(F)F.C([PH+](C(C)(C)C)C(C)(C)C)(C)(C)C>[C:6]([C:5]1[C:4]([F:11])=[CH:3][C:2]([CH2:13][C:14]([O:16][CH3:17])=[O:15])=[C:9]([CH3:10])[CH:8]=1)#[N:7]

Participants

7

Reactant 4

HCID 7943Dimethyl malonateHCID 11430Potassium CarbonateHCID 516893Potassium BicarbonateHCID 341754194-Bromo-2-fluoro-5-methylbenzonitrile

Product 1

HCID 117600964HCID 117600964, compoundYield 43.1%

Reagents, catalysts & solvents 2

HCID 2734635Tri-tert-butylphosphine tetrafluoroborateCatalystHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
170 °C

Procedure

Combined 4-bromo-2-fluoro-5-methylbenzonitrile (4 g, 18.69 mmol) and dimethyl malonate (29.9 mL, 262 mmol). While purging the mixture with nitrogen, added potassium carbonate (3.87 g, 28.0 mmol), potassium hydrogencarbonate (2.81 g, 28.0 mmol), tri-tert-butylphosphonium tetrafluoroborate (0.119 g, 0.411 mmol), and bis(dibenzylidineacetone)palladium (0) (0.118 g, 0.206 mmol). The reaction mixture was heated in an oil bath at 170° C. for 3 hours, then cooled, diluted with ethyl acetate, and filtered through Celite®. The filtrate was concentrated and the residue dissolved in EtOAc, extracted with 1M aqueous sodium hydroxide (2×), twice with 10% aqueous sodium chloride, and brine. The organic phase was dried over sodium sulfate, filtered, and concentrated in vacuo, then purified by flash chromatography to give the title compound (1.67 g, 43%) as a clear colorless oil. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 2.30 (s, 3 H) 3.67 (s, 2 H) 3.72 (s, 3 H) 7.10 (d, J=9.60 Hz, 1 H) 7.42 (d, J=6.32 Hz, 1 H).

Workup

  1. customWhile purging the mixture with nitrogen
  2. temperaturecooled
  3. filtrationfiltered through Celite®
  4. concentrationThe filtrate was concentrated
  5. dissolutionthe residue dissolved in EtOAc
  6. extractionextracted with 1M aqueous sodium hydroxide (2×), twice with 10% aqueous sodium chloride, and brine
  7. dry with materialThe organic phase was dried over sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. custompurified by flash chromatography

Sources & evidence

ORD record
ord-de71ac59248c4d1a9e9d4f006d63121a
Source dataset
uspto-grants-2015_05
Patent number
US09040522B2

Reaction notes

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