2'-Hydroxyacetophenone → 1'-Benzoylspiro[chroman-2,4'-piperidin]-4-one

HRID 1093900Notes

Reaction equation

HRID 1093900 reaction equation
[OH:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8](=[O:10])[CH3:9].[C:11]([N:19]1[CH2:24][CH2:23][C:22](=O)[CH2:21][CH2:20]1)(=[O:18])[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1.N1CCCC1>CO.C(N1CCC(=O)CC1)(=O)C1C=CC=CC=1>[C:11]([N:19]1[CH2:24][CH2:23][C:22]2([CH2:9][C:8](=[O:10])[C:3]3[C:2](=[CH:7][CH:6]=[CH:5][CH:4]=3)[O:1]2)[CH2:21][CH2:20]1)(=[O:18])[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1

Participants

6

Reactant 3

HCID 83752'-HydroxyacetophenoneHCID 31268PyrrolidineHCID 90583N-Benzoyl-4-piperidone

Product 1

HCID 72605101'-Benzoylspiro[chroman-2,4'-piperidin]-4-oneYield 93.8%

Reagents, catalysts & solvents 2

HCID 90583N-Benzoyl-4-piperidoneCatalystHCID 887MethanolSolvent

Procedure

A solution of 2′-hydroxyacetophenone (5, 5.88 mL, 48.85 mmol), 1-benzoyl-4-piperidone (6, 10 g, 49 mmol), and pyrrolidine (4.1 mL, 49 mmol) in 55 mL of methanol was heated in an oil bath at 65° C. After ˜18 hours the oil bath was removed and the solution was allowed to cool to room temperature. Additional 1-benzoyl-4-piperidone (6, 100 mg, 0.5 mmol) was added and heating at 65° C. was resumed. After an additional ˜2.5 hours the oil bath was removed and the solution was allowed to cool to room temperature. This mixture was concentrated under reduced pressure on a rotary evaporator followed by high vacuum to give a viscous, orange oil. This oil was triturated with diethyl ether to provide a solid that was collected by vacuum filtration, washed with diethyl ether, and dried in vacuo at room temperature to afford 1′-benzoylspiro[chroman-2,4′-piperidin]-4-one (7) as an off-white solid (14.72 g, 93.8% yield). The filtrate was evaporated to dryness, triturated with diethyl ether, filtered, washed with diethyl ether, and dried in vacuo at room temperature to afford additional compound 7 as a pale tan solid (0.54 g, 3.7% yield). Both samples were homogeneous by TLC (silica gel, 1.5% methanol in dichloromethane, UV visualization; Rf (7)=0.15−0.2).

Workup

  1. customAfter ˜18 hours the oil bath was removed
  2. temperatureheating at 65° C.
  3. customAfter an additional ˜2.5 hours the oil bath was removed
  4. temperatureto cool to room temperature
  5. concentrationThis mixture was concentrated under reduced pressure on a rotary evaporator
  6. customto give a viscous, orange oil
  7. customThis oil was triturated with diethyl ether
  8. customto provide a solid
  9. filtrationthat was collected by vacuum filtration
  10. washwashed with diethyl ether
  11. customdried in vacuo at room temperature

Sources & evidence

ORD record
ord-102069f835934524ac36a1bad82ece9c
Source dataset
uspto-grants-2012_03
Patent number
US08133695B2

Reaction notes

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