Sodium Iodide → Diisopropyl 2-((1-(trifluoromethyl)cyclopropyl)methyl)malonate

HRID 1049281Notes

Reaction equation

HRID 1049281 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+].[Na+].[I-].CC1C=CC(S(O[CH2:29][C:30]2([C:33]([F:36])([F:35])[F:34])[CH2:32][CH2:31]2)(=O)=O)=CC=1>CN(C=O)C>[F:34][C:33]([F:36])([F:35])[C:30]1([CH2:29][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])[CH2:32][CH2:31]1

Participants

6

Reactant 4

HCID 5238Sodium IodideHCID 24758Sodium hydrideHCID 83223Diisopropyl malonateHCID 24805800HCID 24805800, compound

Product 1

HCID 90403930Diisopropyl 2-((1-(trifluoromethyl)cyclopropyl)methyl)malonateYield 57.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

A 0° C. solution of diisopropyl malonate (4.10 mL, 21.58 mmol) in DMF (30 mL) was treated with NaH (60% in mineral oil, 1.036 g, 25.9 mmol), warmed to RT, treated with NaI (0.647 g, 4.32 mmol) followed by the drop-wise addition of a solution of (1-(trifluoromethyl)cyclopropyl)methyl 4-methylbenzenesulfonate (2.54 g, 8.63 mmol) in DMF (30 mL) and heated at 80° C. overnight. The mixture was cooled to RT, quenched with satd. NH4Cl, extracted with hexane (3×) and the combined organics were dried over Na2SO4, concentrated to dryness and purified via silica gel chromatography (MTBE/Hex) to afford diisopropyl 2-((1-(trifluoromethyl)cyclopropyl)methyl)malonate (1.53 g, 57.1%). 1H NMR (400 MHz, DMSO-d6): δ 4.91 (m, 2H), 3.47 (t, J=7.2 Hz, 1H), 2.10 (d, J=7.2 Hz, 2H), 1.17 (dd, J=7.3, 6.3 Hz, 12H), 0.89 (m, 2H), 0.76 (m, 2H).

Workup

  1. temperatureheated at 80° C. overnight
  2. temperatureThe mixture was cooled to RT
  3. customquenched with satd
  4. extractionNH4Cl, extracted with hexane (3×)
  5. dry with materialthe combined organics were dried over Na2SO4
  6. concentrationconcentrated to dryness
  7. custompurified via silica gel chromatography (MTBE/Hex)

Sources & evidence

ORD record
ord-0e8fb07e582c448fbf00644cfe674f0e
Source dataset
uspto-grants-2016_07
Patent number
US09382228B2

Reaction notes

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