Acetic Acid → HCID 15035838, compound

HRID 1195223Notes

Reaction equation

HRID 1195223 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:8]=[CH:9][C:10]=1[O:11][CH3:12])[CH2:6][NH2:7].[CH2:13]=O.[C:15]([OH:18])(=O)[CH3:16].[CH:19]([N:22]1[CH2:27]C[C:25](=O)[CH2:24][CH2:23]1)([CH3:21])[CH3:20]>CO.O>[CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:8]=[CH:9][C:10]=1[O:11][CH3:12])[CH2:6][N:7]1[CH2:25][CH:24]2[C:15](=[O:18])[CH:16]([CH2:27][N:22]([CH:19]([CH3:21])[CH3:20])[CH2:23]2)[CH2:13]1

Participants

7

Reactant 4

HCID 176Acetic Acid2×HCID 712FormaldehydeHCID 793131-(Isopropyl)-4-piperidoneHCID 79832Veratrylamine

Product 1

HCID 15035838HCID 15035838, compound

Reagents, catalysts & solvents 2

HCID 887MethanolSolvent2×HCID 962WaterSolvent

Procedure

A 200-mL, three-necked, round-bottomed flask was equipped with a magnetic stirrer, a heating mantle, a standard condenser with a N2 inlet, a 50-mL addition funnel, and a glass stopper. A mixture containing 3,4-dimethoxybenzylamine (8.36 g, 50 mmol), paraformaldehyde (3.15 g, 105 mmol) and CH3OH (35 mL) was made acidic with the addition of glacial acetic acid (3.0 g, 50 mmol). Stirring the mixture under N2 for 20 min was followed by the dropwise addition of 1-isopropyl-4-piperidinone (42, 7.06 g, 50 mmol) and glacial acetic acid (3.0 g, 50 mmol) in CH3OH (25 mL) over 1.25 h. Boiling of the mixture was continuous for an additional 23 h. This new mixture was evaporated to give a red viscous oil. After dissolving the oil in H2O (100 mL), the solution was extracted (ether, 2×100 mL), the latter being discarded. Chilling (ice water bath) of the water layer below 10° C., followed by basification (pH~12) with KOH pellets (6.6 g, 100 mmol), produced an orange suspension which was extracted (CH2Cl2, 4×80 mL). Combined extracts were dried (Na2SO4, overnight), filtered, and concentrated to give a crude oil. This oil was digested in 250 mL of Skelly B (bp 60°-68° C.) for 0.5 h and the supernatant was decanted. Evaporation of the solvent gave an oil which, when distilled (175°-205° C./10-4 mm Hg), afforded a yellow oil. Adding Skelly B induced crystallization to give 4.32 g (26%) of off white ketone (23); mp 79.5°-80.5° C. IR (KBr) cm-1 3095, 3015 (Ar--H), 2980, 2955, 2920, 2855, 2810 (C--H), 1745 (C=O), 1620, 1605 (C=C); 1H NMR (DCCl3) δ1.03 (d, 6H, CH3, J=6.6 Hz), 2.59 [bs, 2H, H(1,5)], 2.81-2.90 [m, 5H, ring protons and CH(CH3)2 ], 2.98 (dd, 2H, ring protons, J=10.7 Hz, J'=3.2 Hz), 3.08 (dd, 2H, ring protons, J=10.7 Hz, J'=2.99 Hz), 3.47 (s, 2H, ArCH2), 3.87 (s, 3H, OCH3), 3.88 (s, 3H, OCH3), 6.80-6.92 (m, 3H, Ar--H); 13C NMR (DCCl3) ppm 18.17 (CH3), 46.85 [C(1,5)], 53.40 [CH(CH3)2 ], 53.86 [C(2,4)], 55.76, 55.86 (OCH3), 58.01 [C(6,8)], 60.93 (ArCH2), 110.60, 111.46, 120.68, 131.30, 148.04, 148.90 (Ar--C), 215.27 (C=O); 15N NMR (DCCl3) ppm 39.66 [N(7)], 40.93 [N(3)]. Anal. Calcd. for C19H28N2O3 : C, 68.65; H, 8.49. Found: C, 68.70; H, 8.53.

Workup

  1. customA 200-mL, three-necked, round-bottomed flask was equipped with a magnetic stirrer
  2. additiona heating mantle, a standard condenser with a N2 inlet, a 50-mL addition funnel
  3. waitBoiling of the mixture was continuous for an additional 23 h
  4. customThis new mixture was evaporated
  5. customto give a red viscous oil
  6. extractionthe solution was extracted (ether, 2×100 mL)
  7. temperatureChilling (ice water bath) of the water layer below 10° C.
  8. customproduced an orange suspension which
  9. extractionwas extracted (CH2Cl2, 4×80 mL)
  10. dry with materialCombined extracts were dried (Na2SO4, overnight)
  11. filtrationfiltered
  12. concentrationconcentrated
  13. customto give a crude oil
  14. waitThis oil was digested in 250 mL of Skelly B (bp 60°-68° C.) for 0.5 h
  15. customthe supernatant was decanted
  16. customEvaporation of the solvent
  17. customgave an oil which, when
  18. distillationdistilled (175°-205° C./10-4 mm Hg)
  19. customafforded a yellow oil
  20. additionAdding Skelly B
  21. customcrystallization

Sources & evidence

ORD record
ord-689cb66ae8dc4c2aa168b82c71cddf29
Source dataset
uspto-grants-1992_05
Patent number
US05110933

Reaction notes

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