Ethyl Acetate → HCID 15981605, compound

HRID 327633Notes

Reaction equation

HRID 327633 reaction equation
[NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[CH2:3][CH2:2]1.Cl[CH2:11][CH2:12][CH2:13][OH:14].C(=O)([O-])[O-].[K+].[K+].C(OCC)(=O)C>[Br-].C([N+](CCCC)(CCCC)CCCC)CCC.C(Cl)Cl.O.C1(C)C=CC=CC=1>[OH:14][CH2:13][CH2:12][CH2:11][N:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[CH2:3][CH2:2]1

Participants

9

Reactant 4

HCID 8857Ethyl AcetateHCID 10328IndolineHCID 11430Potassium Carbonate2×HCID 123133-Chloro-1-propanol3×

Product 1

HCID 15981605HCID 15981605, compoundYield 72.5%

Reagents, catalysts & solvents 4

HCID 74236Tetrabutylammonium BromideCatalyst2×HCID 962WaterSolvent2×HCID 1140TolueneSolvent2×HCID 6344DichloromethaneSolvent

Procedure

A stirred reaction mixture consisting of 22.5 ml (0.20 mole) of indoline, 29.8 ml (0.30 mole) of 3-chloropropanol, 41.4 g (0.30 mole) of potassium carbonate, 0.5 g of tetra-n-butylammonium bromide, 150 ml of toluene, and 50 ml of water was heated at reflux temperature for 5 hr. An additional 15 ml (0.15 mole) of 3-chloropropanol was added and reflux continued for an additional 23 hr. Thin layer chromatographic (TLC) analysis (10% ethyl acetate in methylene chloride) showed the reaction to be about 50% complete. Additional potassium carbonate (20 g), tetra-n-butylammonium bromide (0.5 g) and 3-chloropropanol (15 ml) were added to the reaction mixture which was then heated at reflux temperature for another 18 hr. Tlc analysis showed the reaction to be 66% complete. The mixture was diluted with water and toluene. The toluene layer was separated, washed twice with water, and then extracted twice with 2N hydrochloric acid solution. The acid extracts were washed once with toluene and combined. Toluene was added to the acid extract and the mixture basified by agitating while adding 50% sodium hydroxide solution. The organic layer was separated, washed with water, and the wash back extracted with toluene. The toluene solutions were combined, dried (sodium sulfate) and concentrated to give 25.7 g of a dark brown oil which was purified by chromatography on a 380 g column of silica gel using increasing portions of ethyl acetate in methylene chloride to elute the desired product (12.3 g).

Workup

  1. customA stirred reaction mixture
  2. temperaturewas heated
  3. temperatureat reflux temperature for 5 hr
  4. temperaturereflux
  5. customthe reaction
  6. temperaturewas then heated
  7. temperatureat reflux temperature for another 18 hr
  8. customthe reaction
  9. customThe toluene layer was separated
  10. washwashed twice with water
  11. extractionextracted twice with 2N hydrochloric acid solution
  12. washThe acid extracts were washed once with toluene
  13. additionToluene was added to the acid
  14. extractionextract
  15. additionwhile adding 50% sodium hydroxide solution
  16. customThe organic layer was separated
  17. washwashed with water
  18. washthe wash back
  19. extractionextracted with toluene
  20. dry with materialdried (sodium sulfate)
  21. concentrationconcentrated

Sources & evidence

ORD record
ord-a01c18bb25f7415a8386938450e49878
Source dataset
uspto-grants-1993_12
Patent number
US05273993

Reaction notes

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