Sodium hydride → Diallyl 2-[2-(4-cyanophenyl)ethyl]-2-(3,5-difluoro-4-triisopropylsilanyloxybenzyl)malonate

HRID 1921891Notes

Reaction equation

HRID 1921891 reaction equation
[C:1]([C:3]1[CH:8]=[CH:7][C:6]([CH2:9][CH2:10][CH:11]([C:18]([O:20][CH2:21][CH:22]=[CH2:23])=[O:19])[C:12]([O:14][CH2:15][CH:16]=[CH2:17])=[O:13])=[CH:5][CH:4]=1)#[N:2].[H-].[Na+].[F:26][C:27]1[CH:28]=[C:29]([CH:32]=[C:33]([F:46])[C:34]=1[O:35][Si:36]([CH:43]([CH3:45])[CH3:44])([CH:40]([CH3:42])[CH3:41])[CH:37]([CH3:39])[CH3:38])[CH2:30]Br.[Cl-].[NH4+]>O1CCOCC1>[C:1]([C:3]1[CH:8]=[CH:7][C:6]([CH2:9][CH2:10][C:11]([CH2:30][C:29]2[CH:28]=[C:27]([F:26])[C:34]([O:35][Si:36]([CH:40]([CH3:42])[CH3:41])([CH:43]([CH3:45])[CH3:44])[CH:37]([CH3:39])[CH3:38])=[C:33]([F:46])[CH:32]=2)([C:12]([O:14][CH2:15][CH:16]=[CH2:17])=[O:13])[C:18]([O:20][CH2:21][CH:22]=[CH2:23])=[O:19])=[CH:5][CH:4]=1)#[N:2]

Participants

6

Reactant 4

HCID 24758Sodium hydrideHCID 25517Ammonium ChlorideHCID 57971936Diallyl 2-[2-(4-cyanophenyl)ethyl]malonateHCID 579719463,5-Difluoro-4-triisopropylsilanyloxybenzyl bromide

Product 1

HCID 57971937Diallyl 2-[2-(4-cyanophenyl)ethyl]-2-(3,5-difluoro-4-triisopropylsilanyloxybenzyl)malonate

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent2×

Procedure

10 g (31.91 mmol) of diallyl 2-[2-(4-cyanophenyl)ethyl]malonate are dissolved in 250 ml of dioxane and, at 0° C., 1.4 g (35.1 mmol) of 60% sodium hydride are added in portions, and the mixture is stirred at room temperature for 30 min. After renewed cooling to 0° C., a solution of 14.53 g (38.30 mmol) of 3,5-difluoro-4-triisopropylsilanyloxybenzyl bromide in 250 ml of dioxane is added dropwise, and the mixture is stirred while warming to room temperature for 2 h. The reaction solution is then added to 500 ml of saturated ammonium chloride solution and extracted with ethyl acetate. The combined organic phases are dried over sodium sulfate and concentrated. The resulting crude product is purified by flash chromatography on silica gel (mobile phase: cyclohexane/ethyl acetate 10:1→4:1). 14.3 g (73% of theory) of the title compound are obtained.

Workup

  1. temperatureAfter renewed cooling to 0° C.
  2. stirringthe mixture is stirred
  3. temperaturewhile warming to room temperature for 2 h
  4. extractionextracted with ethyl acetate
  5. dry with materialThe combined organic phases are dried over sodium sulfate
  6. concentrationconcentrated
  7. customThe resulting crude product is purified by flash chromatography on silica gel (mobile phase: cyclohexane/ethyl acetate 10:1→4:1)

Sources & evidence

ORD record
ord-2a22e73b50aa48248614c89a9c503699
Source dataset
uspto-grants-2012_05
Patent number
US08173704B2

Reaction notes

Loading…