1-Butanol → HCID 69203597, compound

HRID 1394113Notes

Reaction equation

HRID 1394113 reaction equation
[CH2:1]([O:3][C:4](=[O:20])[CH2:5][C:6]([C:8]1[CH:13]=[CH:12][C:11]([CH:14]2[CH2:19][CH2:18][CH2:17][CH2:16][CH2:15]2)=[CH:10][CH:9]=1)=O)[CH3:2].[NH2:21][C:22]1[CH:31]=[CH:30][C:25]([NH:26][C:27](=[O:29])[CH3:28])=[CH:24][CH:23]=1.[CH2:32](O)[CH2:33]CC>Cl.NC1C=CC(NC(=O)C)=CC=1.O>[CH2:1]([O:3][C:4](=[O:20])[CH:5]=[C:6]([NH:21][C:22]1[CH:23]=[CH:24][C:25]([NH:26][C:27](=[O:29])[CH3:28])=[CH:30][CH:31]=1)[C:8]1[CH:13]=[CH:12][C:11]([CH:14]2[CH2:19][CH2:18][CH2:17][CH2:16][CH2:15]2)=[CH:10][CH:9]=1)[CH2:2][CH2:32][CH3:33]

Participants

6

Reactant 3

HCID 2631-Butanol2×HCID 312304-AminoacetanilideHCID 68884378Ethyl 3-(4-cyclohexylphenyl)-3-oxopropanoate

Product 1

HCID 69203597HCID 69203597, compoundYield 98%

Reagents, catalysts & solvents 2

HCID 1707224-Aminoacetanilide hydrochlorideCatalystHCID 962WaterSolvent

Conditions

Temperature
400 °C

Procedure

Into a 1 liter single-neck round-bottom flask equipped with a Soxhlet extractor apparatus with condenser, magnetic stirrer and nitrogen inlet was placed 50.25 g (0.183 moles) of 3-(4-cyclohexylphenyl)-3-oxo-propionic acid ethyl ester, 25 g (0.167 moles) of 4′-aminoacetanilide, 1.55 g (0.008 moles) 4′-aminoacetanilide hydrochloride salt and 500 mL of dry n-butanol. Into the Soxhlet thimble (33×118 mm) was placed highly activated 4A sieves (1.7-2.4 mm beads). These sieves are activated immediately before use under high vacuum with heating (400° C. for 30 min). The mixture was then brought to reflux such that the butanol azeotropically removed water, driving the equilibrium reaction, and the water was removed from the butanol by the sieves before being returned to the reaction pot. The reaction was allowed to continue for 48 hrs. It was necessary to replace the charge of sieves after the first 24 hrs. Transesterification to the butyl ester along with removal of ethanol occurs concomitantly with enamine formation. After 48 hrs the reaction pot was cooled, then placed in a −40° C. freezer and crystals were allowed to form over 24 hrs. The crystals were collected by vacuum filtration and the solids washed with cold ethanol. The product was then dried in a vacuum oven to give 73.8 g (98%) of the desired enamine.

Workup

  1. customInto a 1 liter single-neck round-bottom flask equipped with a Soxhlet extractor apparatus with condenser, magnetic stirrer and nitrogen inlet
  2. customthe equilibrium reaction
  3. customthe water was removed from the butanol by the sieves
  4. additioncharge of sieves after the first 24 hrs
  5. customTransesterification to the butyl ester along with removal of ethanol
  6. customAfter 48 hrs the reaction
  7. temperaturepot was cooled
  8. customplaced in a −40° C.
  9. customto form over 24 hrs
  10. filtrationThe crystals were collected by vacuum filtration
  11. washthe solids washed with cold ethanol
  12. customThe product was then dried in a vacuum oven

Sources & evidence

ORD record
ord-7473060d52764e9b82fd31be1abb903c
Source dataset
uspto-grants-2008_03
Patent number
US07348340B2

Reaction notes

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