Water → 1-(1-Benzylpiperidin-4-yl)-4-phenylbutan-1-one

HRID 1068134Notes

Reaction equation

HRID 1068134 reaction equation
[C:1]1([CH2:7][CH2:8][CH2:9][CH:10]=[C:11]2[CH2:16][CH2:15][N:14]([CH2:17][C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=3)[CH2:13][CH2:12]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.B.O.S(=O)(=O)(O)[OH:27]>CCOCC.C(OCC)(=O)C>[CH2:17]([N:14]1[CH2:13][CH2:12][CH:11]([C:10](=[O:27])[CH2:9][CH2:8][CH2:7][C:1]2[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=2)[CH2:16][CH2:15]1)[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1

Participants

7

Reactant 4

HCID 962Water2×HCID 1118Sulfuric AcidHCID 6331BoraneHCID 181876891-Benzyl-4-(4-phenylbutylidene)piperidine

Product 1

HCID 181875541-(1-Benzylpiperidin-4-yl)-4-phenylbutan-1-one

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 4-(4-phenylbutylidene)-1-benzylpiperidine (from the Step C) (4.37 g) in anhydrous ether (150 mL) under nitrogen with stirring was add 1M borane solution in TEF (45 mL). The reaction was stirred for 3 h when water (2 mL) was added dropwise. The mixture was stirred a further 30 min and was then cooled in an ice bath. A solution of chromic anhydride (2.5 g), concentrated sulfuric acid (5.44 mL) and water (125 mL) was added dropwise with vigorous magnetic stirring over 5 min. After another 5 min, the ice bath was removed. After 1.5 h at rt, 0.5N sodium hydroxide and ether (400 mL each) were added and the mixture was stirred until the residue dissolved. The layers were separated and the aqueous layer was extracted twice with ether. The combined ether layers were washed with an aqueous EDTA solution, water and brine (100 mL each), dried over sodium sulfate and concentrated under reduced pressure to give a colorless gel. Flash chromatography on silica gel with 30-50% ethyl acetate in hexanes with 3% (v/v) TEA gave the title compound (1 g) as a colorless gel. Rf: 0.43 (30% ethyl acetate in hexanes with 3% (v/v) TEA). 1H NMR (500 MHz, CDCl3): δ7.25-7.33 (m, 7 H), 7.16-7.22 (m, 3 H), 3.51 (s, 2 H), 2.89-2.93 (m, 2 H), 2.63 (t, J=7.6 Hz, 2 H), 2.46 (t, J=7.2 Hz, 2 H), 2.38 (tt, J=11.5 and 3.9 Hz, 1 H), 1.99-2.03 (m, 2 H), 1.92 (tt, J=7.2 and 7.6 Hz, 2 H), 1.76-1.81 (m, 2 H), 1.65-1.72 (m, 2 H).

Workup

  1. additionwas added dropwise
  2. temperaturewas then cooled in an ice bath
  3. stirringmagnetic stirring over 5 min
  4. waitAfter another 5 min
  5. customthe ice bath was removed
  6. waitAfter 1.5 h at rt
  7. addition0.5N sodium hydroxide and ether (400 mL each) were added
  8. stirringthe mixture was stirred until the residue
  9. dissolutiondissolved
  10. customThe layers were separated
  11. extractionthe aqueous layer was extracted twice with ether
  12. washThe combined ether layers were washed with an aqueous EDTA solution, water and brine (100 mL each)
  13. dry with materialdried over sodium sulfate
  14. concentrationconcentrated under reduced pressure
  15. customto give a colorless gel

Sources & evidence

ORD record
ord-8a432121ad5741b2824e541db98bbe05
Source dataset
uspto-grants-2001_06
Patent number
US06248755B1

Reaction notes

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