p-Bromochlorobenzene → HCID 58288432, compound

HRID 1476135Notes

Reaction equation

HRID 1476135 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([Cl:8])=[CH:4][CH:3]=1.[Mg].[CH3:10][C:11](=[C:13]([C:19]([O:21][CH2:22][CH3:23])=[O:20])[C:14]([O:16][CH2:17][CH3:18])=[O:15])[CH3:12]>C(OCC)C.[Cu]Cl>[Cl:8][C:5]1[CH:6]=[CH:7][C:2]([C:11]([CH:13]([C:19]([O:21][CH2:22][CH3:23])=[O:20])[C:14]([O:16][CH2:17][CH3:18])=[O:15])([CH3:10])[CH3:12])=[CH:3][CH:4]=1

Participants

6

Reactant 3

HCID 7806p-Bromochlorobenzene2×HCID 81255Diethyl isopropylidenemalonateHCID 5462224Magnesium

Product 1

HCID 58288432HCID 58288432, compound

Reagents, catalysts & solvents 2

HCID 62652Cuprous chlorideCatalystHCID 3283Diethyl EtherSolvent3×

Procedure

Under argon, 1 g (5.23 mmol) of 1-bromo-4-chlorobenzene in 2.5 ml of diethyl ether was added slowly to 254 mg (10.45 mmol) of magnesium turnings in 5 ml of diethyl ether. After the reaction had started, a further 1 g (5.23 mmol) of 1-bromo-4-chlorobenzene in 2.5 ml of diethyl ether was metered into the reaction mixture. The reaction mixture was stirred at room temperature for 30 min, 103 mg (1.05 mmol) of copper(I) chloride were added and the mixture was then cooled to −10° C. 2.09 g (10.45 mmol) of diethyl propan-2-ylidenemalonate were then slowly added dropwise. The reaction mixture was subsequently heated to reflux and stirred at this temperature for 3 h. 20 ml of ice-cold 1 M hydrochloric acid were then added very slowly. After separation of the phases, the aqueous phase was extracted three more times with diethyl ether. The combined organic phases were dried over magnesium sulphate and then concentrated to dryness. The crude product was purified by preparative HPLC (mobile phase methanol/water 70:30). This gave 800 mg of the title compound (25% of theory).

Workup

  1. temperaturethe mixture was then cooled to −10° C
  2. temperatureThe reaction mixture was subsequently heated
  3. temperatureto reflux
  4. stirringstirred at this temperature for 3 h
  5. customAfter separation of the phases
  6. extractionthe aqueous phase was extracted three more times with diethyl ether
  7. dry with materialThe combined organic phases were dried over magnesium sulphate
  8. concentrationconcentrated to dryness
  9. customThe crude product was purified by preparative HPLC (mobile phase methanol/water 70:30)

Sources & evidence

ORD record
ord-8cb28c241d484edb9e64e1ee90f27c6f
Source dataset
uspto-grants-2015_04
Patent number
US09018414B2

Reaction notes

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