Water → 1-(1-Benzylpiperidin-4-yl)-3-phenyl-1-propanone

HRID 1068129Notes

Reaction equation

HRID 1068129 reaction equation
[C:1]1([CH2:7][CH2:8][CH:9]=[C:10]2[CH2:15][CH2:14][N:13]([CH2:16][C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=3)[CH2:12][CH2:11]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.B.O.S(=O)(=O)(O)[OH:26]>CCOCC.C1COCC1.CCN(CC)CC.CCOC(C)=O>[CH2:16]([N:13]1[CH2:12][CH2:11][CH:10]([C:9](=[O:26])[CH2:8][CH2:7][C:1]2[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=2)[CH2:15][CH2:14]1)[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1

Participants

9

Reactant 4

HCID 962Water2×HCID 1118Sulfuric AcidHCID 6331BoraneHCID 211929951-Benzyl-4-(3-phenylpropylidene)piperidine

Product 1

HCID 211930001-(1-Benzylpiperidin-4-yl)-3-phenyl-1-propanone

Reagents, catalysts & solvents 4

HCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolventHCID 8471TriethylamineSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 1.115 g 4-(3-phenylpropylidene)-1-benzylpiperidine from Step B in 40 mL anhydrous ether under nitrogen was added 11.5 mL 1M borane solution in THF with stirring. After stirring for three hours, 2 mL of water was added dropwise, and the mixture was stirred for 30 min. After cooling with ice, a solution prepared from 0.287 g chromic anhydride, 0.624 mL concentrated sulfuric acid and 15 mL water was added dropwise with vigorous magnetic stirring over 5 minutes. After stirring for an additional 5 minutes, the cooling bath was removed. After 1.5 hours more, 100 mL each of 0.5N NaOH & ether was added, and the mixture was stirred to disolve a solid residue. After separating the layers, the aqueous layer was extracted with 2×100 mL ether. The combined ether layer was washed with 100 mL each of EDTA, water, and saturated brine, dried over Na2SO4, and concentrated under reduced pressure to give a colorless gel. The oxidation step were then repeated with half of the reagent used above. Flash chromatography on silica gel with 30˜50% EtOAc in hexanes with 3% (v/v) Et3N gave 0.293 g of the title compound as a colorless gel. RF: 0.41 (30% EtOAc in hexanes having 3% (v/v) Et3N). 1H NMR (500 MHz, CDCl3): δ7.17˜7.33 (m, ˜10H), 3.51 (s, 2H), 2.88˜2.92 (m, 2H), 2.75˜2.80 (m, 2H), 2.26˜2.32 (m, 1H), 1.98˜2.04 (m, 2H), 1.76˜1.82 (m, 2H), 1.63˜1.72 (m, 4H). ESI-MS 308.1 (M+H), HPLC A: 2.45 min.

Workup

  1. stirringAfter stirring for three hours
  2. stirringthe mixture was stirred for 30 min
  3. temperatureAfter cooling with ice
  4. additionwas added dropwise with vigorous
  5. stirringmagnetic stirring over 5 minutes
  6. stirringAfter stirring for an additional 5 minutes
  7. customthe cooling bath was removed
  8. addition100 mL each of 0.5N NaOH & ether was added
  9. stirringthe mixture was stirred
  10. customAfter separating the layers
  11. extractionthe aqueous layer was extracted with 2×100 mL ether
  12. washThe combined ether layer was washed with 100 mL each of EDTA, water, and saturated brine
  13. dry with materialdried over Na2SO4
  14. concentrationconcentrated under reduced pressure
  15. customto give a colorless gel

Sources & evidence

ORD record
ord-736177eddd3343ad97e8358350890575
Source dataset
uspto-grants-2001_06
Patent number
US06248755B1

Reaction notes

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