Allyl bromide → 2-Ethyl-1-(4-fluoro-phenyl)-2-(morpholin-4-yl)-pent-4-en-1-one

HRID 15248Notes

Reaction equation

HRID 15248 reaction equation
[H-].[Na+].[F:3][C:4]1[CH:9]=[CH:8][C:7]([C:10](=[O:20])[CH:11]([N:14]2[CH2:19][CH2:18][O:17][CH2:16][CH2:15]2)[CH2:12][CH3:13])=[CH:6][CH:5]=1.Br[CH2:22][CH:23]=[CH2:24]>CN(C)C=O>[CH2:12]([C:11]([N:14]1[CH2:15][CH2:16][O:17][CH2:18][CH2:19]1)([CH2:24][CH:23]=[CH2:22])[C:10]([C:7]1[CH:8]=[CH:9][C:4]([F:3])=[CH:5][CH:6]=1)=[O:20])[CH3:13]

Participants

5

Reactant 3

HCID 7841Allyl bromideHCID 24758Sodium hydride2×HCID 190495341-(4-Fluorophenyl)-2-(morpholin-4-yl)-1-butanone

Product 1

HCID 190495862-Ethyl-1-(4-fluoro-phenyl)-2-(morpholin-4-yl)-pent-4-en-1-oneYield 38.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
50 °C

Procedure

56 g of a 50% suspension of sodium hydride in mineral oil (0.22 mol sodium hydride) is added to 100 ml dimethylformamide. 45.2 g (0.16 mol) 1-(4-Fluorophenyl)-2-(morpholin-4-yl)-1-butanone, dissolved in 50 ml diemethylformamide, are added to this suspension dropwise and at room temperature, and subsequently stirred overnight. Then, 19.36 g 1-brom-2-propene are added dropwise. The temperature raises to 50° C. and the solution is kept at this temperature for 16 hours. After cooling, excess sodium hydride is destroyed by the addition of 5 ml isopropanol and the reaction mixture subsequently poured onto an ice/water mixture. The organic products are extracted with ethyl acetate, the combined extracts dried over magnesium sulfate and the solvent evaporated. The crude product thus obtained is purified by chromatography silica gel (eluent: ethyl acetate/petroleum ether 4:1). 2-Ethyl-1-(4-fluoro-phenyl)-2-(morpholin-4-yl)-pent-4-en-1-one (17.8 g, 38%) is obtained as a yellowish oil. 1H-NMR analysis is in agreement with the proposed structure. This compound is used for the next step.

Workup

  1. additionare added to this suspension dropwise
  2. customat room temperature
  3. customsubsequently stirred overnight
  4. temperatureAfter cooling
  5. customexcess sodium hydride is destroyed by the addition of 5 ml isopropanol
  6. additionthe reaction mixture subsequently poured onto an ice/water mixture
  7. extractionThe organic products are extracted with ethyl acetate
  8. dry with materialthe combined extracts dried over magnesium sulfate
  9. customthe solvent evaporated
  10. customThe crude product thus obtained
  11. customis purified by chromatography silica gel (eluent: ethyl acetate/petroleum ether 4:1)

Sources & evidence

ORD record
ord-d3715b2cbe0f4b418c28f7c79da179cb
Source dataset
uspto-grants-2010_06
Patent number
US07732504B2

Reaction notes

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