Sodium hydride → HCID 90110274, compound

HRID 1508768Notes

Reaction equation

HRID 1508768 reaction equation
[C:1]([O:10][CH:11]([CH3:13])[CH3:12])(=[O:9])[CH2:2][C:3]([O:5][CH:6]([CH3:8])[CH3:7])=[O:4].[H-].[Na+].[N+:16]([C:19]1[CH:26]=[CH:25][C:22]([CH2:23]Br)=[CH:21][CH:20]=1)([O-:18])=[O:17]>CN(C=O)C>[N+:16]([C:19]1[CH:26]=[CH:25][C:22]([CH2:23][CH:2]([C:3]([O:5][CH:6]([CH3:7])[CH3:8])=[O:4])[C:1]([O:10][CH:11]([CH3:13])[CH3:12])=[O:9])=[CH:21][CH:20]=1)([O-:18])=[O:17]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 660114-Nitrobenzyl bromideHCID 83223Diisopropyl malonate

Product 1

HCID 90110274HCID 90110274, compoundYield 67.5%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

A 250-mL round bottom flask was charged with diisopropyl malonate (2.09 g, 11.1 mmol) in DMF (24 mL). Sodium hydride (60% suspension, 0.44 g, 11.1 mmol) was slowly added to this solution at 0° C. After 15 minutes, a solution of 4-nitrobenzyl bromide (2.00 g, 9.26 mmol, 1.0 eq.) in DMF (24 mL) was added in one portion and then the reaction was stirred for 19 h. After this time, the reaction was warmed to rt. The reaction was quenched with 2N HCl then diluted in water (300 mL) and extracted with methyl tert-butylether (3×50 mL). The combined extract was washed with saturated sodium chloride (2×25 mL), dried over sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by column chromatography on silica eluting with 9:1 hexanes/ethyl acetate to afford the title compound (2.02 g, 67%) as a colorless oil. MW=323.34. 1H NMR (DMSO-d6, 500 MHz) δ 8.15 (d, J=10.0 Hz, 2H), 7.53 (d, J=9.0 Hz, 2H), 4.88 (septet, J=6.5 Hz, 2H), 3.89 (t, J=8.5 Hz, 1H), 3.19 (d, J=8.5 Hz, 2H), 1.14 (d, J=6.5 Hz, 6H), 1.11 (d, J=6.5 Hz, 6H).

Workup

  1. customThe reaction was quenched with 2N HCl
  2. additionthen diluted in water (300 mL)
  3. extractionextracted with methyl tert-butylether (3×50 mL)
  4. extractionThe combined extract
  5. washwas washed with saturated sodium chloride (2×25 mL)
  6. dry with materialdried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customThe residue was purified by column chromatography on silica eluting with 9:1 hexanes/ethyl acetate

Sources & evidence

ORD record
ord-13463e91804c440b9333078b6792e2e2
Source dataset
uspto-grants-2015_12
Patent number
US09221843B2

Reaction notes

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