Tetrahydrofuran → 1-(4-Phenyl-1-tosylpiperidin-4-yl)butan-1-one

HRID 333424Notes

Reaction equation

HRID 333424 reaction equation
[CH2:1]([Mg]Cl)[CH2:2][CH3:3].[C:6]1([C:12]2([C:28]#N)[CH2:17][CH2:16][N:15]([S:18]([C:21]3[CH:26]=[CH:25][C:24]([CH3:27])=[CH:23][CH:22]=3)(=[O:20])=[O:19])[CH2:14][CH2:13]2)[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1.[O:30]1CCCC1>C1(C)C=CC=CC=1>[C:6]1([C:12]2([C:28](=[O:30])[CH2:1][CH2:2][CH3:3])[CH2:17][CH2:16][N:15]([S:18]([C:21]3[CH:26]=[CH:25][C:24]([CH3:27])=[CH:23][CH:22]=3)(=[O:20])=[O:19])[CH2:14][CH2:13]2)[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1

Participants

5

Reactant 3

HCID 8028TetrahydrofuranHCID 905204-Phenyl-1-(p-tolylsulphonyl)piperidine-4-carbonitrileHCID 178455855HCID 178455855, compound

Product 1

HCID 669878981-(4-Phenyl-1-tosylpiperidin-4-yl)butan-1-oneYield 50%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
67.5 °C

Procedure

88 mL (176 mmol) of n-propylmagnesium chloride are added to a solution of 30 g (88 mmol) of 4-phenyl-1-(toluene-4-sulfonyl)piperidine-4-carbonitrile in 500 mL of toluene. The reaction mixture is stirred for 6 hours at 65-70° C. and then overnight at room temperature. The reaction is stopped by adding 100 mL of tetrahydrofuran, and is then hydrolysed with 1N hydrochloric acid solution and extracted with ethyl acetate. The organic phases are combined and dried over sodium sulfate. The solvents are evaporated off and the residue is then taken up in diethyl ether and filtered off. 1.38 g of starting material are recovered. The filtrate is concentrated to dryness and then chromatographed on silica gel (eluent: 80/20 heptane/ethyl acetate). 17.8 g of 1-[4-phenyl-1-(toluene-4-sulfonyl)piperidin-4-yl]-butan-1-one in the form of a white powder are obtained in a yield of 50%.

Workup

  1. customovernight
  2. customat room temperature
  3. extractionhydrolysed with 1N hydrochloric acid solution and extracted with ethyl acetate
  4. dry with materialdried over sodium sulfate
  5. customThe solvents are evaporated off
  6. filtrationfiltered off
  7. custom1.38 g of starting material are recovered
  8. concentrationThe filtrate is concentrated to dryness
  9. customchromatographed on silica gel (eluent: 80/20 heptane/ethyl acetate)

Sources & evidence

ORD record
ord-84e3a5d43a8a4c01b28c9557b458a806
Source dataset
uspto-grants-2014_11
Patent number
US08877968B2

Reaction notes

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