Sulfuric Acid → 4-(4-Butylpiperidin-1-yl)-1-(2-methylphenyl)butan-1-one

HRID 1723871Notes

Reaction equation

HRID 1723871 reaction equation
I[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1OC.[CH2:10]([CH:14]1[CH2:19][CH2:18][N:17]([CH2:20][CH2:21][CH2:22]C#N)[CH2:16][CH2:15]1)[CH2:11][CH2:12][CH3:13].S(=O)(=O)(O)O.[OH-].[Na+].CC[O:34][CH2:35][CH3:36]>C(Cl)Cl.CO.C1COCC1>[CH2:10]([CH:14]1[CH2:19][CH2:18][N:17]([CH2:20][CH2:21][CH2:22][C:35]([C:36]2[CH:2]=[CH:7][CH:6]=[CH:5][C:4]=2[CH3:3])=[O:34])[CH2:16][CH2:15]1)[CH2:11][CH2:12][CH3:13]

Participants

8

Reactant 5

HCID 1118Sulfuric AcidHCID 3283Diethyl Ether2×HCID 14798Sodium HydroxideHCID 68257o-IodoanisoleHCID 186263854-(4-Butylpiperidin-1-YL)butanenitrile

Product 1

HCID 99483204-(4-Butylpiperidin-1-yl)-1-(2-methylphenyl)butan-1-oneYield 26%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 21226129Dichloromethane methanolSolvent

Procedure

In a 25 mL oven-dried flask was charged Mg turnings (125 mg, 5.2 mmol) which were activated by the use of a heat-gun. Under inert atmosphere was added a suspension of 2-iodoanisole (1.13 g, 5.2 mmol) in Et2O (4 mL) and the reaction mixture was allowed to stand at rt for 1 hour. Compound 4 (720 mg, 3.4 mmol) dissolved in Et2O (4 mL) was added and the mixture was refluxed over-night. THF (15 mL) and sulfuric acid (4 mL, 2 M) was added and the reaction mixture was stirred for 4 h, followed by addition of NaOH (6 mL, 2 M). The reaction mixture was extracted with ethyl acetate (3×50 mL), and the combined organic phases were evaporated to dryness to produce 1.2 g of crude 5. The crude product was subjected to CC [eluent: CH2Cl2:CH3OH (99:1)] to give pure 5 (0.42 g, 26%). 1H NMR (CDCl3) δ0.83 (t, 3H), 1.20-1.42 (m, 9H), 1.65-1.73 (d, 2H), 1.96-2.20 (m, 4H), 2.53 (t, 2H), 3.02-3.17 (m, 4H), 3.89 (s, 3H), 6.95-7.01 (m, 2H), 7.44 (t, 1H), 7.65 (d, 1H).

Workup

  1. customIn a 25 mL oven-dried flask
  2. additionUnder inert atmosphere was added
  3. additionwas added
  4. temperaturethe mixture was refluxed over-night
  5. extractionThe reaction mixture was extracted with ethyl acetate (3×50 mL)
  6. customthe combined organic phases were evaporated to dryness
  7. customto produce 1.2 g of crude 5

Sources & evidence

ORD record
ord-294c49c62ed34e0cbe75497ddd8cb515
Source dataset
uspto-grants-2009_02
Patent number
US07485651B2

Reaction notes

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