4-Iodotoluene → HCID 11208981, compound

HRID 1170035Notes

Reaction equation

HRID 1170035 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].I[C:19]1[CH:24]=[CH:23][C:22]([CH3:25])=[CH:21][CH:20]=1.[Cl-].[NH4+]>O1CCOCC1.[Cu]Br.CN(P(N(C)C)(N(C)C)=O)C>[C:14]([O:13][C:3](=[O:12])[CH:4]([C:19]1[CH:24]=[CH:23][C:22]([CH3:25])=[CH:21][CH:20]=1)[C:5]([O:7][C:8]([CH3:9])([CH3:10])[CH3:11])=[O:6])([CH3:17])([CH3:16])[CH3:15]

Participants

8

Reactant 4

HCID 122074-IodotolueneHCID 24758Sodium hydrideHCID 25517Ammonium ChlorideHCID 68324Di-tert-butyl malonate

Product 1

HCID 11208981HCID 11208981, compoundYield 55.2%

Reagents, catalysts & solvents 3

HCID 24593copper(I) bromideCatalystHCID 12679HexamethylphosphoramideSolventHCID 312751,4-DioxaneSolvent

Procedure

To the suspension of sodium hydride (60%, 1.2 g, 30 mmol) in 50 ml of anhydrous dioxane containing 3.5 ml of HMPA were added di-tert-butyl malonate (6.488 g, 30 mmol) and p-iodotoluene (1), the mixture was stirred at room temperature for 1 hour. To the resulting solution was added copper (I) bromide (5.163 g, 36 mmol, 1.2 equivalents), the mixture was heated at refluxing temperature. Then the reaction mixture was cooled to room temperature, 30 ml of saturated aqueous ammonium chloride solution was added to quench the reaction, and the product was extracted with ethyl acetate (50 ml×3), washed with brine, dried over sodium sulfate. The solvent was evaporated, and the oily residue obtained was purified by chromatography to give p-tolyl-malonic acid di-tert-butyl ester 5.072 g (yield 55.2%) as a white solid. 1H NMR (CDCl3) δ: 7.275 (2H, d, J=8.06 Hz), 7.161 (2H, d, J=8.05 Hz), 4.397 (1H, s), 2.344 (3H, s), 1.471 (18H, s) ppm. FABMS (+Ve), m/z 307 [MH+], 251 [MH+−C4H8], 195 [MH+−2C4H8]. Anal. calcd. for C18H26O4: C, 70.6; H, 8.6. Found: C, 70.34; H, 8.62.

Workup

  1. temperaturethe mixture was heated
  2. temperatureat refluxing temperature
  3. temperatureThen the reaction mixture was cooled to room temperature
  4. customto quench
  5. customthe reaction
  6. extractionthe product was extracted with ethyl acetate (50 ml×3)
  7. washwashed with brine
  8. dry with materialdried over sodium sulfate
  9. customThe solvent was evaporated
  10. customthe oily residue obtained
  11. customwas purified by chromatography

Sources & evidence

ORD record
ord-334eddbad0d047b4967312d9735268a8
Source dataset
uspto-grants-2010_11
Patent number
US07825216B2

Reaction notes

Loading…