Sodium hydride → HCID 59760045, compound

HRID 1879133Notes

Reaction equation

HRID 1879133 reaction equation
[H-].[Na+].[C:3]([O:16][CH2:17][CH3:18])(=[O:15])[CH2:4][C:5]([O:7][CH2:8][C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1)=[O:6].F[C:20]1[CH:25]=[CH:24][C:23]([N+:26]([O-:28])=[O:27])=[C:22]([CH3:29])[CH:21]=1>CN(C=O)C>[CH3:29][C:22]1[CH:21]=[C:20]([CH:4]([C:5]([O:7][CH2:8][C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)=[O:6])[C:3]([O:16][CH2:17][CH3:18])=[O:15])[CH:25]=[CH:24][C:23]=1[N+:26]([O-:28])=[O:27]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 949565-Fluoro-2-nitrotolueneHCID 562228Benzyl ethyl malonate

Product 1

HCID 59760045HCID 59760045, compoundYield 175.6%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

Sodium Hydride (19.09 g, 477 mmol) was added portionwise over 30 minutes to an ice cooled solution of ethyl phenylmethyl propanedioate (115 ml, 477 mmol) in DMF (500 ml). Upon complete addition, the reaction was allowed to warm to room temperature. After stirring for 30 minutes, a solution of 4-fluoro-2-methyl-1-nitrobenzene (30 ml, 239 mmol) in DMF (250 ml) was added, the reaction heated to 100° C. and stirred at this temperature for 16 hours under an atmosphere of argon. The reaction was then left to stand at room temperature for 72 hours. The reaction was quenched with concentrated HCl (˜100 ml) with stirring and cooling (ice bath), diluted with ethyl acetate (2 L), washed with water (3×2 L), brine (1 L), dried over sodium sulfate, filtered and concentrated to give a dark yellow oil (˜150 g). Purification was by silica chromatography, 1500 g cartridge, sample loaded as a toluene solution to the pre-conditioned column). A gradient of 0 to 5% acetone in pentane eluted the higher running component, this was followed by a gradient of 5 to 15% acetone in isohexane to elute the excess benzyl ethyl malonate and required product. Product-containing fractions were concentrated to give the title compound as a pale yellow oil (71.21 g). MS (ES−) [C19H19NO6—H]− 356. 1H-NMR (400 MHz, d6-DMSO) δ 1.14 (3H, t, J 7), 2.50 (3H, s), 4.01-4.21 (2H, m), 5.14-5.25 (2H, m), 5.27 (1H, s), 7.28-7.49 (7H, m), 8.00 (1H, d, J 8)

Workup

  1. additionUpon complete addition
  2. temperaturethe reaction heated to 100° C.
  3. stirringstirred at this temperature for 16 hours under an atmosphere of argon
  4. waitThe reaction was then left
  5. waitto stand at room temperature for 72 hours
  6. customThe reaction was quenched with concentrated HCl (˜100 ml)
  7. stirringwith stirring
  8. temperaturecooling (ice bath)
  9. additiondiluted with ethyl acetate (2 L)
  10. washwashed with water (3×2 L), brine (1 L)
  11. dry with materialdried over sodium sulfate
  12. filtrationfiltered
  13. concentrationconcentrated

Sources & evidence

ORD record
ord-f20c566c5fd24e29b0b1ed85b0f388be
Source dataset
uspto-grants-2012_11
Patent number
US08314147B2

Reaction notes

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