Water → HCID 57995528, compound

HRID 385361Notes

Reaction equation

HRID 385361 reaction equation
[C:1]([O:9][CH2:10][CH3:11])(=[O:8])[CH2:2][C:3]([O:5][CH2:6][CH3:7])=[O:4].[H-].[Na+].F[C:15]1[CH:16]=[C:17]([O:30][CH2:31][C:32]([F:35])([F:34])[F:33])[C:18]([N+:27]([O-:29])=[O:28])=[C:19]([O:21][CH2:22][C:23]([F:26])([F:25])[F:24])[CH:20]=1.O>CN(C=O)C>[CH2:10]([O:9][C:1](=[O:8])[CH:2]([C:15]1[CH:16]=[C:17]([O:30][CH2:31][C:32]([F:34])([F:35])[F:33])[C:18]([N+:27]([O-:29])=[O:28])=[C:19]([O:21][CH2:22][C:23]([F:24])([F:26])[F:25])[CH:20]=1)[C:3]([O:5][CH2:6][CH3:7])=[O:4])[CH3:11]

Participants

6

Reactant 4

HCID 962WaterHCID 7761Diethyl MalonateHCID 24758Sodium hydrideHCID 57995656HCID 57995656, compound

Product 1

HCID 57995528HCID 57995528, compoundYield 81.6%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Conditions

Temperature
25 °C

Procedure

To a solution of diethyl malonate (18.0 g, 114.9 mmol) in DMF (50 mL) was added sodium hydride (60% in mineral oil, 3.0 g, 125.0 mmol) at 0° C. The reaction mixture was stirred at 25° C. for 0.5 h and a solution of 5-fluoro-2-nitro-1,3-bis-(2,2,2-trifluoro-ethoxy)-benzene (18.0 g, 53.4 mmol) in DMF (30 mL) was added dropwise. The reaction mixture was heated 100° C. for 24 h. After cooling the reaction mixture was poured into water (300 mL) and extracted with EtOAc (3×50 mL). The combined organic phases were washed with water (3×100 mL), brine (100 mL) and dried (MgSO4). Evaporation of the solvent under reduced pressure gave 2-[4-nitro-3,5-bis-(2,2,2-trifluoro-ethoxy)-phenyl]-malonic acid diethyl ester as a brown oil (20.8 g, 80%). The crude product was used for the next step without purification. 1H NMR (300 MHz, CDCl3/TMS): δ 6.91 (s, 2H), 4.62 (s, 1H), 4.48 (q, J=8.0 Hz, 4H), 4.28-4.16 (m, 4H), 1.31-1.25 (m, 6H). 13C NMR (75 MHz, CDCl3/TMS): δ 166.4, 149.2, 136.7, 132.3, 122.3 (q, 1JCF=276.6 Hz), 109.5 (two signals), 67.0 (q, 2JCF=36.7 Hz), 61.4, 41.6, 14.0.

Workup

  1. temperatureThe reaction mixture was heated 100° C. for 24 h
  2. temperatureAfter cooling the reaction mixture
  3. extractionextracted with EtOAc (3×50 mL)
  4. washThe combined organic phases were washed with water (3×100 mL), brine (100 mL)
  5. dry with materialdried (MgSO4)
  6. customEvaporation of the solvent under reduced pressure

Sources & evidence

ORD record
ord-46be85a2d0cc41a8b43537a796ac98cb
Source dataset
uspto-grants-2013_02
Patent number
US08367863B2

Reaction notes

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