Hydrochloric Acid → 1-Benzyl-4-(3-phenylpropylidene)piperidine

HRID 1068128Notes

Reaction equation

HRID 1068128 reaction equation
C[Si]([N-][Si](C)(C)C)(C)C.[K+].[Br-].[C:12]1([CH2:18][CH2:19][CH2:20][P+](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1.[CH2:40]([N:47]1[CH2:52][CH2:51][C:50](=O)[CH2:49][CH2:48]1)[C:41]1[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=1.Cl>C1(C)C=CC=CC=1>[CH2:40]([N:47]1[CH2:52][CH2:51][C:50](=[CH:20][CH2:19][CH2:18][C:12]2[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=2)[CH2:49][CH2:48]1)[C:41]1[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 192201-Benzyl-4-piperidoneHCID 3251421Potassium bis(trimethylsilyl)amideHCID 109286473-Phenylpropyl triphenylphosphonium bromide

Product 1

HCID 211929951-Benzyl-4-(3-phenylpropylidene)piperidineYield 62.5%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent3×

Procedure

A solution of 100 mL of 0.5M potassium bis(trimethylsilyl)amide in toluene was added to a mixture of 23.07 g (3-phenylpropyl)triphenylphosphonium bromide from Step A in 150 mL toluene in an ice bath over 15 minute with stirring under nitrogen. After stirring for 15 more minutes, a solution of 8.515 g of 1-benzyl-4-piperidone in 50 mL toluene was added over 30 minutes with stirring. The reaction mixture was stirred as it was allowed to warm to room temperature overnight. After 15 hours, the reaction mixture was poured into 200 mL cold 1N HCl. The layers were separated and the toluene layer was washed with 2×200 mL 1N HCl. The combined HCl solution and an oily interfacial layer was washed with 100 mL toluene. After adding 30 g KOH, the aqueous layer was extraced with 3×150 mL of ether. The combined ether solution was washed with 100 mL each of water and saturated brine, dried over Na2SO4, filtered, and concentrated under reduced pressure. The residue was purified by silica gel flash chromatography using 10˜15% ethyl acetate in hexanes having 3% (v/v) Et3N to give 8.2 g of the title compound as a colorless oil. RF: 0.38 (10% EtOAc in hexanes having 3% (v/v) Et3N). 1H NMR (500 MHz, CDCl3): δ7.34 (d, 4.3 Hz, 4H), 7.25˜7.30 (m, 2H), 7.17˜7.21 (m, 4H), 5.19 (t, 7.2 Hz, 1H), 3.51 (s, 3H), 2.64˜2.67 (m, 2H), 2.41˜2.44 (m, 2H), 2.29˜2.35 (m, 4H), 2.18˜2.22 (m, 4H).

Workup

  1. stirringAfter stirring for 15 more minutes
  2. stirringwith stirring
  3. stirringThe reaction mixture was stirred as it
  4. customThe layers were separated
  5. washthe toluene layer was washed with 2×200 mL 1N HCl
  6. washThe combined HCl solution and an oily interfacial layer was washed with 100 mL toluene
  7. additionAfter adding 30 g KOH
  8. washThe combined ether solution was washed with 100 mL each of water and saturated brine
  9. dry with materialdried over Na2SO4
  10. filtrationfiltered
  11. concentrationconcentrated under reduced pressure
  12. customThe residue was purified by silica gel flash chromatography

Sources & evidence

ORD record
ord-d51f5eed4c1b48c59b64f6c68354766a
Source dataset
uspto-grants-2001_06
Patent number
US06248755B1

Reaction notes

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