1-Benzyl-4-piperidone → 1-benzyl-2'-(4-methoxybenzyl)-2'H-spiro[piperidine-4,5'-pyrano[3,2-c]pyrazol]-7'(6'H)-one

HRID 2284353Notes

Reaction equation

HRID 2284353 reaction equation
[OH:1][C:2]1[C:3]([C:16](=[O:18])[CH3:17])=[N:4][N:5]([CH2:7][C:8]2[CH:13]=[CH:12][C:11]([O:14][CH3:15])=[CH:10][CH:9]=2)[CH:6]=1.[CH2:19]([N:26]1[CH2:31][CH2:30][C:29](=O)[CH2:28][CH2:27]1)[C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1.N1CCCC1>CO>[CH2:19]([N:26]1[CH2:31][CH2:30][C:29]2([O:1][C:2]3[C:3](=[N:4][N:5]([CH2:7][C:8]4[CH:9]=[CH:10][C:11]([O:14][CH3:15])=[CH:12][CH:13]=4)[CH:6]=3)[C:16](=[O:18])[CH2:17]2)[CH2:28][CH2:27]1)[C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1

Participants

5

Reactant 3

HCID 192201-Benzyl-4-piperidoneHCID 31268PyrrolidineHCID 668354041-(4-hydroxy-1-(4-methoxybenzyl)-1H-pyrazol-3-yl)ethanone

Product 1

HCID 668354691-benzyl-2'-(4-methoxybenzyl)-2'H-spiro[piperidine-4,5'-pyrano[3,2-c]pyrazol]-7'(6'H)-oneYield 72.2%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

Suspended 1-(4-hydroxy-1-(4-methoxybenzyl)-1H-pyrazol-3-yl)ethanone (350 mg, 1.42 mmol) in 10 mL methanol and added N-benzyl-4-piperidone (0.25 mL, 1.42 mmol) and pyrrolidine (0.036 mL, 0.3 eq). The mixture was then heated at reflux for 18 h. The reaction was then cooled to room temperature and methanol was removed under reduced pressure. The resultant orange oil was partitioned between 50 mL ethyl acetate and 50 mL water. The aqueous phase was extracted with an additional 50 mL ethyl acetate. The organic layers were combined and dried over sodium sulfate, filtered and concentrated. The resultant oil was flash chromatographed (50-100% ethyl acetate/heptane gradient, 25 g silica) to yield 428 mg (72%) of 1-benzyl-2′-(4-methoxybenzyl)-2′H-spiro[piperidine-4,5′-pyrano[3,2-c]pyrazol]-7′(6′H)-one as a pale yellow solid. 1H NMR (400 MHz, CDCl3) δ ppm 7.25-7.37 (m, 6H), 6.95 (s, 1H), 6.81-6.92 (m, 2H), 5.20 (s, 2H), 3.79 (s, 3H), 3.49 (s, 2H), 2.63 (s, 2H), 2.57 (d, J=11.3 Hz, 2H), 2.25-2.44 (m, 2H), 2.02 (d, J=12.5 Hz, 2H), 1.62-1.77 (m, 2H); m/z (M+1)=418.5.

Workup

  1. temperatureThe mixture was then heated
  2. temperatureat reflux for 18 h
  3. custommethanol was removed under reduced pressure
  4. customThe resultant orange oil was partitioned between 50 mL ethyl acetate and 50 mL water
  5. extractionThe aqueous phase was extracted with an additional 50 mL ethyl acetate
  6. dry with materialdried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customchromatographed (50-100% ethyl acetate/heptane gradient, 25 g silica)

Sources & evidence

ORD record
ord-c33de267836e48d28266133c5a352af8
Source dataset
uspto-grants-2015_09
Patent number
US09145416B2

Reaction notes

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