Sodium hydride → HCID 66756606, compound

HRID 1642629Notes

Reaction equation

HRID 1642629 reaction equation
[H-].[Na+].[C:3]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])(=[O:10])[CH2:4][C:5]([O:7][CH2:8][CH3:9])=[O:6].[CH2:16]([O:23][C:24]1[CH:29]=[C:28](F)[CH:27]=[CH:26][C:25]=1[N+:31]([O-:33])=[O:32])[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1>CN(C=O)C>[CH2:8]([O:7][C:5](=[O:6])[CH:4]([C:28]1[CH:27]=[CH:26][C:25]([N+:31]([O-:33])=[O:32])=[C:24]([O:23][CH2:16][C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[CH:29]=1)[C:3]([O:11][C:12]([CH3:14])([CH3:13])[CH3:15])=[O:10])[CH3:9]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 96345tert-Butyl ethyl malonateHCID 110969082-(Benzyloxy)-4-fluoro-1-nitrobenzene

Product 1

HCID 66756606HCID 66756606, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
50 °C

Procedure

To a suspension of NaH (60%, 9.38 g, 235 mmol) in DMF (200 mL) at 0° C. under N2 is added tert-butyl ethyl malonate (45.7 mL, 243 mmol) over 30 min. The reaction is stirred for 1.5 h in an ice bath. 2-Benzyloxy-4-fluoro-1-nitrobenzene (20.0 g, 80.9 mmol) is added and the reaction heated to 50° C. for 7.5 h. The reaction is quenched with H2O (600 mL) and extracted with EtOAc (2 L). The organic phase is concentrated to ˜1 L, washed with H2O (2×500 mL) and brine (300 mL), and dried over Na2SO4. Evaporation yields a yellow oil. The oil is azeotroped with DCM and the resulting solid is triturated with a hexanes/Et2O solution, affording a yellow solid. Two additional crops of the solid are obtained from the filtrate upon standing. The solids are combined to afford 2-(3-benzyloxy-4-nitrophenyl) -malonic acid tert-butyl ester ethyl ester: MS (M−H)−=414.

Workup

  1. customThe reaction is quenched with H2O (600 mL)
  2. extractionextracted with EtOAc (2 L)
  3. concentrationThe organic phase is concentrated to ˜1 L
  4. washwashed with H2O (2×500 mL) and brine (300 mL)
  5. dry with materialdried over Na2SO4
  6. customEvaporation
  7. customyields a yellow oil
  8. customThe oil is azeotroped with DCM
  9. customthe resulting solid is triturated with a hexanes/Et2O solution
  10. customaffording a yellow solid
  11. customTwo additional crops of the solid are obtained from the filtrate

Sources & evidence

ORD record
ord-f0f13318728c49c8a4c1d3b21f9b79d9
Source dataset
uspto-grants-2012_02
Patent number
US08119666B2

Reaction notes

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