Acetic Acid → HCID 86678048, compound

HRID 1852325Notes

Reaction equation

HRID 1852325 reaction equation
[CH2:1]([NH:3][CH2:4][CH3:5])[CH3:2].[CH2:6](O)[C:7]#[CH:8].[C:10]([CH2:12][C:13]([O:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH3:23])=[O:14])#[N:11].C(O)(=O)C>C1(C)C=CC=CC=1.[O-2].[O-2].[Mn+4].ClCCl>[C:10](/[C:12](=[CH:6]\[CH:7]=[CH:8]\[N:3]([CH2:4][CH3:5])[CH2:1][CH3:2])/[C:13]([O:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH3:23])=[O:14])#[N:11]

Participants

8

Reactant 4

HCID 176Acetic AcidHCID 7859Propargyl alcoholHCID 8021Diethylamine2×HCID 4384482Octyl cyanoacetate

Product 1

HCID 86678048HCID 86678048, compoundYield 72%

Reagents, catalysts & solvents 3

HCID 178418406HCID 178418406, compoundCatalystHCID 1140TolueneSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
52 °C

Procedure

Diethylamine (14.5 ml, 0.14 mol) and propargyl alcohol (6.81 ml, 0.117 mol) are dissolved in 100 ml of toluene. 34.5 g of manganese dioxide (activated, <5 μm; 3.4 equiv.) are added portionwise while controlling the strong exotherm (temperature <50° C.) and the mixture is left stirring at 52° C. for 20 hours. The reaction mixture is filtered. The yellow filtrate is poured into a reactor surmounted by a Dean and Stark apparatus. n-Octyl cyanoacetate (23 g, 0.117 mol) and catalyst (0.1 equiv., 0.667 ml of acetic acid and 1.2 ml of N,N-diethylamine) are added with stirring and the reaction mixture is brought to reflux. It is left at reflux for 5 hours 30 minutes. After cooling, dichloromethane is added and washing is carried out once with a saturated sodium bicarbonate solution and then once with water. The organic phase is dried and then concentrated under vacuum. The brown red oil obtained is chromatographed on a silica column (gradient of eluents: heptane/AcOEt 90:10 to 80:20). 26 g (yield: 72%) of the pure fractions of the derivative of Example 4 are thus obtained in the form of an orange-coloured gum which crystallizes; recrystallization from heptane gave the derivative of Example 4 in the form of a yellow powder:

Workup

  1. customthe strong exotherm (temperature <50° C.)
  2. waitthe mixture is left
  3. filtrationThe reaction mixture is filtered
  4. additionThe yellow filtrate is poured into a reactor
  5. stirringwith stirring
  6. temperatureto reflux
  7. waitIt is left
  8. temperatureat reflux for 5 hours 30 minutes
  9. temperatureAfter cooling
  10. washwashing
  11. customThe organic phase is dried
  12. concentrationconcentrated under vacuum
  13. customThe brown red oil obtained
  14. customis chromatographed on a silica column (gradient of eluents: heptane/AcOEt 90:10 to 80:20)
  15. custom26 g (yield: 72%) of the pure fractions of the derivative of Example 4 are thus obtained in the form of an orange-coloured gum which
  16. customcrystallizes
  17. customrecrystallization from heptane
  18. customgave the derivative of Example 4 in the form of a yellow powder

Sources & evidence

ORD record
ord-1806513cd1294bff89a3a56f8dd754ef
Source dataset
uspto-grants-2015_02
Patent number
US08961941B2

Reaction notes

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