Aniline → HCID 5275755, compound

HRID 1394289Notes

Reaction equation

HRID 1394289 reaction equation
[CH2:1]([CH:8]1[CH2:13][CH2:12][NH:11][CH2:10][CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH:14]([CH:16]=[CH2:17])=O.[NH2:18][C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].[OH-].[Na+]>C1COCC1.C1CCN2C(=NCCC2)CC1>[CH2:1]([CH:8]1[CH2:13][CH2:12][N:11]([CH2:17][CH2:16][CH2:14][NH:18][C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)[CH2:10][CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

8

Reactant 5

HCID 6115AnilineHCID 7847AcroleinHCID 14798Sodium HydroxideHCID 317384-BenzylpiperidineHCID 5049666Sodium triacetoxyborohydride

Product 1

HCID 5275755HCID 5275755, compoundYield 66%

Reagents, catalysts & solvents 2

HCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneCatalystHCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of 4-benzylpiperidine (52.58 g, 300 mmol), DBU (0.449 ml, 3.0 mmol) in THF (600 ml) was added dropwise a solution of acrolein (90%, 18.69 g, 300 mmol) in THF (60 ml) over a period of 10 minutes at −20° C. under stirring. While a temperature of the solution was elevated from −20° C. to −10° C., the solution was stirred 1 hour. To the solution were added at −10° C. aniline (27.94 g, 300 mmol) and sodium triacetoxyborohydride (127.16 g, 600 mmol), successively, and the mixture was stirred for 19 hours while the temperature of the mixture was elevated to room temperature. To the mixture was added an aqueous solution of 2N-sodium hydroxide (900 ml) under ice cooling, and the mixture was stirred for 30 minutes and extracted with diethyl ether (400 ml, 200 ml×2). The organic layer was dried over magnesium sulfate and concentrated under reduced pressure. The concentrate was dissolved in 2-propanol (400 ml), and to the solution was added 4N-hydrogen chloride in ethyl acetate (200 ml) with stirring. The resulting precipitates were collected by filtration. The precipitates were washed with 2-propanol (100 ml×3), and dried under reduced pressure to give the titled compound (75.66 g, 198 mmol, Yield 66%) as white crystals. mp 217° C. (dec.)

Workup

  1. customwas elevated from −20° C. to −10° C.
  2. stirringthe solution was stirred 1 hour
  3. stirringsuccessively, and the mixture was stirred for 19 hours while the temperature of the mixture
  4. customwas elevated to room temperature
  5. stirringthe mixture was stirred for 30 minutes
  6. extractionextracted with diethyl ether (400 ml, 200 ml×2)
  7. dry with materialThe organic layer was dried over magnesium sulfate
  8. concentrationconcentrated under reduced pressure
  9. dissolutionThe concentrate was dissolved in 2-propanol (400 ml)
  10. additionto the solution was added 4N-hydrogen chloride in ethyl acetate (200 ml)
  11. stirringwith stirring
  12. customThe resulting precipitates
  13. filtrationwere collected by filtration
  14. washThe precipitates were washed with 2-propanol (100 ml×3)
  15. customdried under reduced pressure

Sources & evidence

ORD record
ord-1c8fd7affe714853bb2d46d6abe6a395
Source dataset
uspto-grants-2008_03
Patent number
US07348324B2

Reaction notes

Loading…