Acetic Acid → HCID 23195023, compound

HRID 1983429Notes

Reaction equation

HRID 1983429 reaction equation
C[O:2][C:3]1[CH:8]=[C:7]([O:9]C)[CH:6]=[CH:5][C:4]=1[CH2:11][CH2:12][CH2:13][CH2:14][C:15]([OH:17])=[O:16].Br.[C:19](O)(=O)C>>[OH:2][C:3]1[CH:8]=[C:7]([OH:9])[CH:6]=[CH:5][C:4]=1[CH2:11][CH2:12][CH2:13][CH2:14][C:15]([O:17][CH3:19])=[O:16]

Participants

4

Reactant 3

HCID 176Acetic AcidHCID 260Hydrogen BromideHCID 74719765-(2,4-dimethoxyphenyl)pentanoic acid

Product 1

HCID 23195023HCID 23195023, compoundYield 55%

Procedure

A 1 liter 3 neck round-bottomed flask was charged with 35.7 g (150 mmols) of the 5-(2,4-dimethoxyphenyl)-pentanoic acid (4a) and a stir bar. The flask was set into a suitably sized heating mantle supported on a stirring plate with a strong stirring magnet. The flask was fitted with a thermometer, reflux condenser, and argon inlet. Then 400 ml of acetic acid was added via the thermometer port. The mixture was stirred and warmed to dissolve the solid. This was followed by addition of 68 ml (600 mmols) of 48% aqueous hydrobromic acid. The thermometer was replaced and the flask was flushed with argon. With the cooling water on, the flask was heated to reflux. The reflux was maintained for 16 hours, the mixture was cooled and concentrated on a rotary evaporator. 1 L of methanol was added, and HCl was bubbled in for 5 minutes with a sparger, at a moderate rate. The warm solution was allowed to cool and evaporated. The resulting syrup dissolved in 200 ml of ethyl acetate. The solution was washed with 100 ml water, twice with 100 ml of saturated sodium bicarbonate and once with saturated sodium chloride. The organic layer was dried over sodium sulfate and evaporated to a syrup. The crude product was purified on silica eluting with 3:1 to 2:1 hexane-ethyl acetate. Concentration of the pure product fractions afforded 18.5 g (55%) of desired product. 1H NMR (DMSO-d6) δ: 9.01 (s, 1H), 8.92 (s, 1H), 6.75 (d, J=8.2 Hz, 1H), 6.23 (d, J=2 Hz, 1H), 6.10 (dd, J1=2 Hz, J2=8.2 Hz, 1H), 3.56 (s, 3H), 2.37 (t, J=7 Hz, 2H), 2.29 (t, J=7 Hz, 2H), 1.48 (m, 4H).

Workup

  1. temperaturea suitably sized heating mantle
  2. customThe flask was fitted with a thermometer
  3. temperaturereflux condenser, and argon inlet
  4. temperaturewarmed
  5. dissolutionto dissolve the solid
  6. customthe flask was flushed with argon
  7. temperatureWith the cooling water on, the flask was heated to reflux
  8. temperatureThe reflux was maintained for 16 hours
  9. temperaturethe mixture was cooled
  10. concentrationconcentrated on a rotary evaporator
  11. addition1 L of methanol was added
  12. customHCl was bubbled in for 5 minutes with a sparger, at a moderate rate
  13. temperatureto cool
  14. customevaporated
  15. dissolutionThe resulting syrup dissolved in 200 ml of ethyl acetate
  16. washThe solution was washed with 100 ml water, twice with 100 ml of saturated sodium bicarbonate and once with saturated sodium chloride
  17. dry with materialThe organic layer was dried over sodium sulfate
  18. customevaporated to a syrup
  19. customThe crude product was purified on silica eluting with 3:1 to 2:1 hexane-ethyl acetate

Sources & evidence

ORD record
ord-85618a8e7e04485b940658f404ea9d2e
Source dataset
uspto-grants-2009_06
Patent number
US07541454B2

Reaction notes

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