Dimethyl malonate → HCID 86705577, compound

HRID 2279594Notes

Reaction equation

HRID 2279594 reaction equation
[C:1]([O:8][CH3:9])(=[O:7])[CH2:2][C:3]([O:5][CH3:6])=[O:4].I[CH2:11][CH2:12][C@H:13]([O:19][Si:20]([CH2:25][CH3:26])([CH2:23][CH3:24])[CH2:21][CH3:22])[C:14]([O:16][CH2:17][CH3:18])=[O:15].[H-].[Na+]>C1COCC1>[CH2:23]([Si:20]([CH2:21][CH3:22])([CH2:25][CH3:26])[O:19][C@H:13]([C:14]([O:16][CH2:17][CH3:18])=[O:15])[CH2:12][CH2:11][CH:2]([C:1]([O:8][CH3:9])=[O:7])[C:3]([O:5][CH3:6])=[O:4])[CH3:24]

Participants

5

Reactant 3

HCID 7943Dimethyl malonate2×HCID 24758Sodium hydrideHCID 86705576HCID 86705576, compound2×

Product 1

HCID 86705577HCID 86705577, compoundYield 41%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

A solution of dimethyl malonate (6.155 ml, 53.72 mmol), (S)-ethyl 4-iodo-2-(triethylsilyloxy)butanoate (10.00 g, 26.86 mmol) and THF (100 mL), dimethyl malonate, (S)-ethyl 4-iodo-2-(triethylsilyloxy)butanoate (10.00 g, 26.86 mmol) was cooled to −78° C. and maintained under N2. To the solution was added sodium hydride (2.149 g, 53.72 mmol, 60% dispersion in mineral oil) portion wise over 5 min and the resulting mixture stirred at −78° C. for 3 h. The reaction was warmed to RT and stirred for 48 h. The reaction was quenched by adding H2O and extracted with EtOAc. The organic extract was dried (Na2SO4), filtered and concentrated in vacuo. The crude product was purified by SiO2 chromatography eluting with EtOAc/hexane (4:1) to afford 4.2 g, (41%) of (S)-4-ethyl 1,1-dimethyl 4-(triethylsilyloxy)butane-1,1,4-tricarboxylate (398).

Workup

  1. temperaturemaintained under N2
  2. temperatureThe reaction was warmed to RT
  3. stirringstirred for 48 h
  4. customThe reaction was quenched
  5. additionby adding H2O
  6. extractionextracted with EtOAc
  7. extractionThe organic extract
  8. dry with materialwas dried (Na2SO4)
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo
  11. customThe crude product was purified by SiO2 chromatography
  12. washeluting with EtOAc/hexane (4:1)

Sources & evidence

ORD record
ord-9923edf5a46e4d5d93f35b28ae8f7cfa
Source dataset
uspto-grants-2015_09
Patent number
US09133187B2

Reaction notes

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