Sodium hydride → tert-Butyl Methyl [3-Cyano-5-(trifluoromethyl)pyridin-2-yl]malonate

HRID 132842Notes

Reaction equation

HRID 132842 reaction equation
[H-].[Na+].[C:3]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])(=[O:9])[CH2:4][C:5]([O:7][CH3:8])=[O:6].Cl[C:16]1[C:21]([C:22]#[N:23])=[CH:20][C:19]([C:24]([F:27])([F:26])[F:25])=[CH:18][N:17]=1>O1CCCC1>[C:22]([C:21]1[C:16]([CH:4]([C:5]([O:7][CH3:8])=[O:6])[C:3]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])=[N:17][CH:18]=[C:19]([C:24]([F:27])([F:25])[F:26])[CH:20]=1)#[N:23]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 2733872tert-Butyl methyl malonateHCID 200715992-Chloro-5-(trifluoromethyl)nicotinonitrile

Product 1

HCID 59017435tert-Butyl Methyl [3-Cyano-5-(trifluoromethyl)pyridin-2-yl]malonate

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Procedure

To a suspension of sodium hydride (7.8 g, 200 mmol) in tetrahydrofuran (100 mL) under nitrogen was added dropwise a solution of tert-butyl methyl malonate (20 mL, 120 mmol) in anhydrous tetrahydrofuran (100 mL) via syringe. The reaction mixture was stirred for 0.5 h before a solution of the intermediate prepared in Step D above (20.1 g, 97.6 mmol) in tetrahydrofuran (200 mL) was added slowly via syringe. The reaction was stirred at room temperature overnight, then quenched with a saturated solution of ammonium chloride. The organic layer was separated and the aqueous layer was extracted with three portions of ethyl acetate. The combined organic layers were washed with water, dried over sodium sulfate and concentrated in vacuo. Flash chromatography afforded the title compound. 1H NMR (500 MHz, CDCl3) δ 9.03 (d, J=1.5 Hz, 1H), 8.25 (d, J=2.0 Hz, 1H), 5.25 (s, 1H), 3.86 (s, 3M), 1.52 (s, 9H).

Workup

  1. additionwas added slowly via syringe
  2. customquenched with a saturated solution of ammonium chloride
  3. customThe organic layer was separated
  4. extractionthe aqueous layer was extracted with three portions of ethyl acetate
  5. washThe combined organic layers were washed with water
  6. dry with materialdried over sodium sulfate
  7. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-fef84aaac92d44189596f810a0cb5672
Source dataset
uspto-grants-2008_06
Patent number
US07388019B2

Reaction notes

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