1,4-Dioxane → HCID 178420347, compound

HRID 421617Notes

Reaction equation

HRID 421617 reaction equation
[CH2:1]([N:8]([C@@H:16]1[CH2:21][CH2:20][C@H:19]([CH2:22][OH:23])[CH2:18][CH2:17]1)[CH2:9][C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Cl.ClCC[N:28]1[CH2:33][CH2:32][CH2:31][CH2:30][CH2:29]1.[H-].[K+].O1CCO[CH2:38][CH2:37]1>>[CH2:9]([N:8]([CH2:1][C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1)[C@H:16]1[CH2:21][CH2:20][C@@H:19]([CH2:22][O:23][CH2:37][CH2:38][CH:33]2[CH2:32][CH2:31][CH2:30][CH2:29][NH:28]2)[CH2:18][CH2:17]1)[C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1

Participants

5

Reactant 4

HCID 312751,4-Dioxane2×HCID 74826Piperidine, 1-(2-chloroethyl)-, hydrochlorideHCID 82127Potassium hydride2×HCID 178520975HCID 178520975, compound

Product 1

HCID 178420347HCID 178420347, compoundYield 72%

Procedure

cis-{4-[N,N-Dibenzylamino]cyclohexyl}methan-1-ol (2.851 g, 9.21 mmol) and (2-chloroethyl)piperidine hydrochloride were suspended in 50 mL of dioxane. Potassium hydride (3.16 g, 35% by weight in mineral oil) was added dropwise in suspension in 20 mL of dioxane. The reaction mixture was stirred at room temperature for about 1 hour. The reaction mixture was then warmed to about 70° C. and one equivalent of potassium hydride (1.05 g, 35% by weight in mineral oil) was added dropwise. The temperature was maintained for about 2 hours, after which the conversion was complete. The reaction was cooled to room temperature and quenched with methanol. Solvents were removed under reduced pressure. Acetonitrile was added (200 mL) and the gray brown solid was removed by filtration. The crude was purified by column chromatography on silica gel using 3% (ethanol/ammonium hydroxide=8:1) in dichloromethane. The product was isolated as an orange oil that solidified under vacuum. (2.84 g, 72% yield): ES-MS (m/z) 421.

Workup

  1. temperatureThe reaction mixture was then warmed to about 70° C.
  2. temperatureThe temperature was maintained for about 2 hours
  3. temperatureThe reaction was cooled to room temperature
  4. customquenched with methanol
  5. customSolvents were removed under reduced pressure
  6. additionAcetonitrile was added (200 mL)
  7. customthe gray brown solid was removed by filtration
  8. customThe crude was purified by column chromatography on silica gel using 3% (ethanol/ammonium hydroxide=8:1) in dichloromethane
  9. customThe product was isolated as an orange oil that solidified under vacuum

Sources & evidence

ORD record
ord-a3c5d9365486470da6e0bb59c306f571
Source dataset
uspto-grants-2012_01
Patent number
US08101588B2

Reaction notes

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