Hydrochloric Acid → Diethyl 2-(2-(benzyloxy)ethyl)malonate

HRID 514631Notes

Reaction equation

HRID 514631 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].[CH2:14]([O:21][CH2:22][CH2:23]Br)[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1.Cl>O1CCCC1>[CH2:14]([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])[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 7761Diethyl MalonateHCID 24758Sodium hydrideHCID 73833Benzene, ((2-bromoethoxy)methyl)-

Product 1

HCID 12549951Diethyl 2-(2-(benzyloxy)ethyl)malonateYield 90.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

506 mg (60% in oil, 13 mmol equivalents) of sodium hydride was added to 5.0 mL of tetrahydrofuran, and the mixture was cooled to about 0° C. in an ice bath. 3.2 mL (20.7 mmol equivalents) of diethyl malonate was added thereto (solution A). 2.3 g (10.7 mmol equivalents) of 2-benzyloxy-1-bromoethane was dissolved in 3.0 mL of tetrahydrofuran, this was added dropwise to solution A over 10 minutes, and the mixture was refluxed while heating overnight. After completion of the reaction, a 0.5 mol/L aqueous solution of hydrochloric acid was added dropwise to the reaction liquid, and the mixture was extracted three times with diethyl ether. The combined diethyl ether layers were washed with brine, then dried with anhydrous magnesium sulfate, and subsequently concentrated under vacuum, and the obtained crude product was purified by silica gel column chromatography (eluent: hexane/ethyl acetate (v/v)=20/1) to give 2.85 g (9.67 mmol equivalents) of diethyl 2-(2-benzyloxyethyl)malonate.

Workup

  1. temperaturethe mixture was refluxed
  2. temperaturewhile heating overnight
  3. customAfter completion of the reaction
  4. extractionthe mixture was extracted three times with diethyl ether
  5. washThe combined diethyl ether layers were washed with brine
  6. dry with materialdried with anhydrous magnesium sulfate
  7. concentrationsubsequently concentrated under vacuum
  8. customthe obtained crude product
  9. customwas purified by silica gel column chromatography (eluent: hexane/ethyl acetate (v/v)=20/1)

Sources & evidence

ORD record
ord-16621d2bbf0e4bb493233f7fb6ea4bc1
Source dataset
uspto-grants-2015_08
Patent number
US09107964B2

Reaction notes

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