Ethyl Acrylate → HCID 131724221, compound

HRID 481015Notes

Reaction equation

HRID 481015 reaction equation
Br[C:2]1[CH:16]=[CH:15][CH:14]=[CH:13][C:3]=1[CH2:4][O:5][CH2:6][CH2:7][N:8]1[CH2:12][CH2:11][CH2:10][CH2:9]1.[C:17]([O:21][CH2:22][CH3:23])(=[O:20])[CH:18]=[CH2:19].C(=O)([O-])[O-].[K+].[K+]>[Br-].C([N+](CCCC)(CCCC)CCCC)CCC.C1(C)C=CC=CC=1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C1(C)C=CC=CC=1P(C1C=CC=CC=1C)C1C=CC=CC=1C>[N:8]1([CH2:7][CH2:6][O:5][CH2:4][C:3]2[CH:13]=[CH:14][CH:15]=[CH:16][C:2]=2/[CH:19]=[CH:18]/[C:17]([O:21][CH2:22][CH3:23])=[O:20])[CH2:12][CH2:11][CH2:10][CH2:9]1

Participants

8

Reactant 3

HCID 8821Ethyl AcrylateHCID 11430Potassium CarbonateHCID 18765923HCID 18765923, compound

Product 1

HCID 131724221HCID 131724221, compoundYield 69%

Reagents, catalysts & solvents 4

HCID 74236Tetrabutylammonium BromideCatalystHCID 80271Tri-o-tolylphosphineCatalystHCID 167845palladium(II) acetateCatalystHCID 1140TolueneSolvent

Procedure

A mixture of 1-{2-[(2-bromobenzyl)oxy]ethyl}pyrrolidine (11.3 g, 39.7 mmol), ethyl acrylate (8.6 ml, 79.4 mmol), potassium carbonate (13.7 g, 99.3 mmol), tetra-n-butylammonium bromide (12.8 g, 39.7 mmol), tri-o-tolylphosphine (483 mg, 1.59 mmol) and palladium acetate (178 mg, 0.79 mmol) in toluene (40 ml) was stirred at room temperature. The resulting mixture was degassed under reduced pressure and replaced with nitrogen. The mixture was stirred at 100° C. under nitrogen atmosphere for 15 h. After cooling to room temperature, the catalyst was filtered through a pad of celite, and filter cake was washed with toluene then ethyl acetate. The filtrate was evaporated in vacuo and the residue was dissolved with ethyl acetate-hexane (1:1)(200 ml)-2N HCl aq. (50 ml). The aqueous layer was separated and the organic layer was extracted with 2N HCl aq. (40 ml). The combined aqueous layers were basified to pH 9-10 with 2N NaOH aq. at 0° C. and extracted with ethyl acetate-hexane (1:1)(×3). The combined solution was washed with water, brine and dried over MgSO4. After filtration, the filtrate was concentrated in vacuo to give crude product (dark orange oil), which was purified by column chromatography on NH2 silica gel (500 g) (hexane/ethyl acetate 5/1-3/1 as eluent) to afford the titled compound (8.27 g, 69.0%) as a yellow oil.

Workup

  1. customThe resulting mixture was degassed under reduced pressure
  2. stirringThe mixture was stirred at 100° C. under nitrogen atmosphere for 15 h
  3. temperatureAfter cooling to room temperature
  4. filtrationthe catalyst was filtered through a pad of celite
  5. filtrationfilter cake
  6. washwas washed with toluene
  7. customThe filtrate was evaporated in vacuo
  8. dissolutionthe residue was dissolved with ethyl acetate-hexane (1:1)(200 ml)-2N HCl aq. (50 ml)
  9. customThe aqueous layer was separated
  10. extractionthe organic layer was extracted with 2N HCl aq. (40 ml)
  11. customwere basified to pH 9-10 with 2N NaOH aq. at 0° C.
  12. extractionextracted with ethyl acetate-hexane (1:1)(×3)
  13. washThe combined solution was washed with water, brine
  14. dry with materialdried over MgSO4
  15. filtrationAfter filtration
  16. concentrationthe filtrate was concentrated in vacuo
  17. customto give crude product (dark orange oil), which
  18. customwas purified by column chromatography on NH2 silica gel (500 g) (hexane/ethyl acetate 5/1-3/1 as eluent)

Sources & evidence

ORD record
ord-6f75fd9c09f94c0492f5e1a168783263
Source dataset
uspto-grants-2003_11
Patent number
US06653313B2

Reaction notes

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