Toluene → 1-(1-Benzylpiperidin-4-yl)ethanone

HRID 1068138Notes

Reaction equation

HRID 1068138 reaction equation
[CH2:1]([N:8]1[CH2:13][CH2:12][CH:11]([C:14](N(C)OC)=[O:15])[CH2:10][CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH3:20][Mg]Br.C1COCC1.C1(C)C=CC=CC=1>CCOCC>[CH2:1]([N:8]1[CH2:13][CH2:12][CH:11]([C:14](=[O:15])[CH3:20])[CH2:10][CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

6

Reactant 4

HCID 1140TolueneHCID 8028TetrahydrofuranHCID 211930301-benzyl-N-methoxy-N-methylpiperidine-4-carboxamideHCID 178418573HCID 178418573, compound

Product 1

HCID 9109231-(1-Benzylpiperidin-4-yl)ethanone

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent

Procedure

A solution of 47.32 g 1-benzyl-N-methyl-N-methoxy-piperidine-4-carboxamide in 1.5 L anhydrous ether in a 2-L 3-neck round-bottom flask fitted with a nitrogen bubbler, an overhead stirrer, and an addition funnel was cooled with an ice-acetone bath, and was treated with 270 mL of a 1.53M solution of methylmagnesium bromide in 1:3 THF:toluene with stirring over 70 minutes. After stirring in an ice bath for additional two hours, the mixture was quenched with 15 mL EtOAc, stirred for 10 minutes, and then poured into 2 L of ice water. After adjusting the pH to 8˜9, the layers were separated. The mixture was extracted with 4×250 mL ether, the combined ether solution was washed with 300 mL each of water and saturated brine, and then dried over Na2SO4. Removal of solvent under reduced pressure gave 40.68 g of crude product. This material was purified by flash chromatography on silica gel eluting with 25%˜40% EtOAc in hexanes with 1% Et3N to give 39.533 g of the title compound as a yellowish liquid. RF: 0.20 (20% EtOAc in hexanes with 1% (v/v) Et3N). 1H NMR (500 MHz, CDCl3): δ7.32˜7.35 (m, 4H), 7.25˜7.30 (m, 1H), 3.53 (s, 2H), 2.91˜2.95 (m, 2H), 2.28˜2.34 (m, 1H), 2.16 (s, 3H), 2.01˜2.07 (m, 2H), 1.83˜1.88 (m, 2H), 1.66˜1.74 (m, 2H).

Workup

  1. temperaturewas cooled with an ice-acetone bath
  2. customthe mixture was quenched with 15 mL EtOAc
  3. stirringstirred for 10 minutes
  4. additionpoured into 2 L of ice water
  5. customthe layers were separated
  6. extractionThe mixture was extracted with 4×250 mL ether
  7. washthe combined ether solution was washed with 300 mL each of water and saturated brine
  8. dry with materialdried over Na2SO4
  9. customRemoval of solvent under reduced pressure
  10. customgave 40.68 g of crude product
  11. customThis material was purified by flash chromatography on silica gel eluting with 25%˜40% EtOAc in hexanes with 1% Et3N

Sources & evidence

ORD record
ord-d43d680c75044a678a33ad3fd1f15cb0
Source dataset
uspto-grants-2001_06
Patent number
US06248755B1

Reaction notes

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