Water → Di-tert-butyl (4-cyano-2,5-difluorophenyl)propanedioate

HRID 1519526Notes

Reaction equation

HRID 1519526 reaction equation
[H-].[Na+].[C:3]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])(=[O:12])[CH2:4][C:5]([O:7][C:8]([CH3:11])([CH3:10])[CH3:9])=[O:6].[F:18][C:19]1[CH:26]=[C:25](F)[C:24]([F:28])=[CH:23][C:20]=1[C:21]#[N:22].O>CN(C=O)C>[C:14]([O:13][C:3](=[O:12])[CH:4]([C:25]1[CH:26]=[C:19]([F:18])[C:20]([C:21]#[N:22])=[CH:23][C:24]=1[F:28])[C:5]([O:7][C:8]([CH3:9])([CH3:10])[CH3:11])=[O:6])([CH3:17])([CH3:16])[CH3:15]

Participants

6

Reactant 4

HCID 962WaterHCID 24758Sodium hydrideHCID 68324Di-tert-butyl malonateHCID 5938132,4,5-Trifluorobenzonitrile

Product 1

HCID 86694453Di-tert-butyl (4-cyano-2,5-difluorophenyl)propanedioateYield 188.7%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

To a suspension of NaH (2.6 g, 64 mmol, and 60.0% dispersion in oil) in DMF (80 mL) was added a solution of di-tert-butyl malonate (3.57 g, 16.50 mmol) in DMF (20 mL) at 0° C. and this was stirred for 15 min. Subsequently, 2,4,5-trifluorobenzonitrile (3.0 g, 15.0 mmol) was added in one portion and the reaction mixture was stirred for 8 h at 80° C. and three hours at room temperature. Water (50 mL) was added and the aqueous layer was extracted with EtOAc (2×100 mL). The combined organic extracts were washed with water (50 mL) and brine (50 mL), dried over MgSO4 and filtered. After evaporation in vacuo, the residue was purified by flash chromatography (20% EtOAc in hexane) to give 10.0 g of di-tert-butyl(4-cyano-2,5-difluorophenyl)propanedioate as a colorless oil. 1H NMR (500 MHz, CDCl3) δ 7.51 (dd, J=5.5, J=5.4 Hz, 1H), 7.37 (dd, J=5, J=6 Hz, 1H), 4.84 (s, 1H), 1.50 (s, 18H). LC-MS (IE, m/z): 298.2 [(M+1)]+-t-Bu].

Workup

  1. stirringthe reaction mixture was stirred for 8 h at 80° C. and three hours at room temperature
  2. extractionthe aqueous layer was extracted with EtOAc (2×100 mL)
  3. washThe combined organic extracts were washed with water (50 mL) and brine (50 mL)
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. customAfter evaporation in vacuo
  7. customthe residue was purified by flash chromatography (20% EtOAc in hexane)

Sources & evidence

ORD record
ord-75e6ac8926354b968f91822d338e8ccc
Source dataset
uspto-grants-2015_07
Patent number
US09073882B2

Reaction notes

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