Diethyl Malonate → Diethyl 2-(2-(4-bromophenoxy)ethyl)malonate

HRID 1054873Notes

Reaction equation

HRID 1054873 reaction equation
[H-].[Na+].[C:3]([O:11][CH2:12][CH3:13])(=[O:10])[CH2:4][C:5]([O:7][CH2:8][CH3:9])=[O:6].[Br:14][C:15]1[CH:20]=[CH:19][C:18]([O:21][CH2:22][CH2:23]Br)=[CH:17][CH:16]=1>O1CCCC1>[Br:14][C:15]1[CH:20]=[CH:19][C:18]([O:21][CH2:22][CH2:23][CH:4]([C:5]([O:7][CH2:8][CH3:9])=[O:6])[C:3]([O:11][CH2:12][CH3:13])=[O:10])=[CH:17][CH:16]=1

Participants

5

Reactant 3

HCID 7761Diethyl MalonateHCID 24758Sodium hydrideHCID 877972-Bromoethyl p-bromophenyl ether

Product 1

HCID 79459661Diethyl 2-(2-(4-bromophenoxy)ethyl)malonateYield 114.7%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

To a solution of NaH (0.160 g, 6.68 mmol) in anhydrous tetrahydrofuran (20 mL) was added diethyl malonate (1.07 g, 6.68 mmol) dropwise at 0° C. The resulting colorless solution was stirred at 0° C. for 15 minutes, then at room temperature for 30 minutes before cooling again to 0° C. A solution of 1-bromo-4-(2-bromoethoxy)benzene (1.70 g, 6.07 mmol) in anhydrous tetrahydrofuran (10 mL) was added over 5 minutes. The resulting mixture was heated at reflux until complete as judged by TLC. The mixture was cooled to room temperature and carefully quenched with water and then extracted with ethyl acetate (4×50 mL). The combined organic phases were dried over sodium sulfate filtered and concentrated under reduced pressure to give the title compound (2.5 g) as a colorless oil which was used in the next step without purification. 1H NMR (400 MHz, CDCl3) ppm 7.43-7.32 (m, 2H), 6.84-6.68 (m, 2H), 4.32-4.14 (m, 4H), 4.01 (m, 2H), 3.64 (m, 1H), 2.43-2.32 (m, 2H), 1.33-1.18 (m, 6H).

Workup

  1. temperatureat room temperature for 30 minutes before cooling again to 0° C
  2. temperatureThe resulting mixture was heated
  3. temperatureat reflux until complete
  4. temperatureThe mixture was cooled to room temperature
  5. customcarefully quenched with water
  6. extractionextracted with ethyl acetate (4×50 mL)
  7. dry with materialThe combined organic phases were dried over sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-6b8b9c80fa2146fc97f6150ae35cb6f9
Source dataset
uspto-grants-2016_07
Patent number
US09394285B2

Reaction notes

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