2-chloroethyl(dimethyl)sulfanium;iodide

Conditions: temp:45.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 54 g of 2',4'-dichloro-2-(3-pyridyl)-acetophenone are added portionwise under an inert gas to a suspension of 46.5 g of freshly sublimed potassium tert.butylate in 590 ml of tert.butanol and the reaction mixture is stirred at 45° C. for 2 hours. The mixture is treated at room temperature with 59.5 g of 2-chloroethyl-dimethylsulphonium iodide and a spatula tip of sodium iodide and the mixture is held at 50° C. for 16 hours while stirring vigorously. The mixture is poured into water and extracted three times with 300 ml of diethyl ether each time. The combined organic extracts are washed with water, dried over anhydrous sodium sulphate and evaporated under reduced pressure. The residue is chromatographed on silica gel with diethyl ether as the eluent and crystallized from diethyl ether/n-hexane. There are obtained 41.7 g of 2,4-dichlorophenyl 1-(3-pyridyl)-cyclopropyl ketone as white crystals, m.p. 83° C. while stirring vigorously extracted three times with 300 ml of diethyl ether each time The combined organic extracts are washed with water dried over anhydrous sodium sulphate evaporated under reduced pressure The residue is chromatographed on silica gel with diethyl ether as the eluent crystallized from diethyl ether/n-hexane

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of potassium tert-butoxide (3.26 g, 27.6 mmol) in tert-butanol (40 mL) was treated with tert-butyl 4-oxopiperidine-1-carboxylate (5 g, 25.09 mmol), causing the reaction to turn bright orange. The mixture was stirred for 1 h, then treated with (2-chloroethyl)dimethylsulfonium iodide (5.70 g, 22.59 mmol), added in three portions at 10 minute intervals. This addition caused the color of the reaction to gradually fade to pale yellow. The mixture was stirred for 2 hours, then diluted with tert-butanol (10 mL), treated with potassium tert-butoxide (2.96 g, 25.09 mmol), and stirred overnight at room temperature. The reaction was poured into water (100 mL) and extracted 3× with 100 mL ethyl acetate. The combined organic phases were washed with water and brine, then dried over sodium sulfate and concentrated in-vacuo. The residue was purified over a 5×15 cm silica gel column, eluting with ethyl acetate/hexanes (10%-15%-20%-25% EtOAc, 1 L at each concentration), to yield the title compound (1.15 g, 5.10 mmol, 20.34% yield) as a colorless oil. the reaction added in three portions at 10 minute intervals This addition the color of the reaction The mixture was stirred for 2 hours stirred overnight at room temperature extracted 3× with 100 mL ethyl acetate The combined organic phases were washed with water and brine dried over sodium sulfate concentrated in-vacuo The residue was purified over a 5×15 cm silica gel column eluting with ethyl acetate/hexanes (10%-15%-20%-25% EtOAc, 1 L at each concentration),

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a suspension of potassium tert-butoxide (3.48 g) in tert-butanol (32 mL) was added cycloheptanone (1.9 mL) while stirring under nitrogen atmosphere, followed by stirring the mixture at room temperature for 0.5 hour. Then, to the reaction mixture was added (2-chloroethyl)-dimethylsulfonium iodide (3.7 g) in eight portions over 1.6 hours, followed by stirring the mixture at room temperature for 16.5 hours. To the reaction mixture was added water, followed by extraction with diethyl ether. The organic layer was washed with saturated brine, dried and concentrated. The residue was purified by column chromatography on silica gel (diethyl ether:hexane (volume ratio)=1:15) to give spiro[2.6]nonan-4-one (1.40 g). by stirring the mixture at room temperature for 0.5 hour by stirring the mixture at room temperature for 16.5 hours followed by extraction with diethyl ether The organic layer was washed with saturated brine dried concentrated The residue was purified by column chromatography on silica gel (diethyl ether:hexane (volume ratio)=1:15)

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 4-Oxo-piperidine-1-carboxylic acid tert-butyl ester (1.0 g, 5 mmol) was dissolved in tBuOH (10 ml) with tBuOK (1.1 g, 10 mmol) and stirred for 15 minutes before portionwise addition of (2-chloro-ethyl)-dimethyl-sulfonium iodide (Tet. Lett. 1984, 25, 5501) (1.1 g, 5 mmol) over 1 h. The reaction was stirred for 16 h after which time it was partioned between water and CH2Cl2, the organic collected, dried (Na2SO4) and concentrated. Flash column chromatography (EtOAc:n-heptane 1:9-3:7) afforded the titled product (0.2 g, 19%) as a colourless oil. MS: 130.1 (MH+). the organic collected, dried (Na2SO4) concentrated

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of potassium tert-butoxide (3.26 g, 27.6 mmol) in tert-butanol (40 mL) was treated with tert-butyl 4-oxopiperidine-1-carboxylate (5 g, 25.09 mmol), causing the reaction to turn bright orange. The mixture was stirred for 1 h, then treated with (2-chloroethyl)dimethylsulfonium iodide (5.70 g, 22.59 mmol), added in three portions at 10 minute intervals. This addition caused the color of the reaction to gradually fade to pale yellow. The mixture was stirred for 2 hours, then diluted with tert-butanol (10 mL), treated with potassium tert-butoxide (2.96 g, 25.09 mmol), and stirred overnight at room temperature. The reaction was poured into water (100 mL) and extracted 3× with 100 mL ethyl acetate. The combined organic phases were washed with water and brine, then dried over sodium sulfate and concentrated in-vacuo. The residue was purified over a 5×15 cm silica gel column, eluting with ethyl acetate/hexanes (10%-15%-20%-25% EtOAc, 1 L at each concentration), to yield the title compound (1.15 g, 5.10 mmol, 20.34% yield) as a colorless oil. the reaction added in three portions at 10 minute intervals This addition the color of the reaction The mixture was stirred for 2 hours stirred overnight at room temperature extracted 3× with 100 mL ethyl acetate The combined organic phases were washed with water and brine dried over sodium sulfate concentrated in-vacuo The residue was purified over a 5×15 cm silica gel column eluting with ethyl acetate/hexanes (10%-15%-20%-25% EtOAc, 1 L at each concentration),

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 7-bromo-1-tetralone (1.03 g, 4.58 mmol) in tert-butanol (10 mL) was added sodium iodide (0.131 g, 0.872 mmol) and sodium hydride (0.349 g, 60% suspension in mineral oil, 8.72 mmol). The reaction mixture was stirred at r.t. for 20 min. Then (2-chloroethyl)dimethylsulfonium iodide (Intermediate 5, 1.10 g, 4.36 mmol) was added portionwise over 1 h. After the reaction had reached completion, water (15 mL) was added and the resulting mixture was extracted with EtOAc (3×15 mL). The combined organic layers were dried with sodium sulfate, filtered and concentrated in vacuo. The product was purified by flash chromatography using 5% EtOAc in heptanes as eluent to give the title compound (0.789 g, 78%). 1H NMR (400 MHz, CDCl3) δ ppm 0.84 (dd, 2 H), 1.40 (dd, 2 H), 1.95 (t, 2 H), 2.93 (t, 2 H), 7.14 (d, 1 H), 7.55 (dd, 1 H), 8.11 (d, 1 H); MS (ES+) m/z 250.98, 253.03 [M+H]+. was added the resulting mixture was extracted with EtOAc (3×15 mL) The combined organic layers were dried with sodium sulfate filtered concentrated in vacuo The product was purified by flash chromatography

Conditions: temp:45.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 54 g of 2',4'-dichloro-2-(3-pyridyl)-acetophenone are added portionwise under an inert gas to a suspension of 46.5 g of freshly sublimed potassium tert.butylate in 590 ml of tert.butanol and the reaction mixture is stirred at 45° C. for 2 hours. The mixture is treated at room temperature with 59.5 g of 2-chloroethyl-dimethylsulphonium iodide and a spatula tip of sodium iodide and the mixture is held at 50° C. for 16 hours while stirring vigorously. The mixture is poured into water and extracted three times with 300 ml of diethyl ether each time. The combined organic extracts are washed with water, dried over anhydrous sodium sulphate and evaporated under reduced pressure. The residue is chromatographed on silica gel with diethyl ether as the eluent and crystallized from diethyl ether/n-hexane. There are obtained 41.7 g of 2,4-dichlorophenyl 1-(3-pyridyl)-cyclopropyl ketone as white crystals, m.p. 83° C. while stirring vigorously extracted three times with 300 ml of diethyl ether each time The combined organic extracts are washed with water dried over anhydrous sodium sulphate evaporated under reduced pressure The residue is chromatographed on silica gel with diethyl ether as the eluent crystallized from diethyl ether/n-hexane

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of potassium tert-butoxide (3.26 g, 27.6 mmol) in tert-butanol (40 mL) was treated with tert-butyl 4-oxopiperidine-1-carboxylate (5 g, 25.09 mmol), causing the reaction to turn bright orange. The mixture was stirred for 1 h, then treated with (2-chloroethyl)dimethylsulfonium iodide (5.70 g, 22.59 mmol), added in three portions at 10 minute intervals. This addition caused the color of the reaction to gradually fade to pale yellow. The mixture was stirred for 2 hours, then diluted with tert-butanol (10 mL), treated with potassium tert-butoxide (2.96 g, 25.09 mmol), and stirred overnight at room temperature. The reaction was poured into water (100 mL) and extracted 3× with 100 mL ethyl acetate. The combined organic phases were washed with water and brine, then dried over sodium sulfate and concentrated in-vacuo. The residue was purified over a 5×15 cm silica gel column, eluting with ethyl acetate/hexanes (10%-15%-20%-25% EtOAc, 1 L at each concentration), to yield the title compound (1.15 g, 5.10 mmol, 20.34% yield) as a colorless oil. the reaction added in three portions at 10 minute intervals This addition the color of the reaction The mixture was stirred for 2 hours stirred overnight at room temperature extracted 3× with 100 mL ethyl acetate The combined organic phases were washed with water and brine dried over sodium sulfate concentrated in-vacuo The residue was purified over a 5×15 cm silica gel column eluting with ethyl acetate/hexanes (10%-15%-20%-25% EtOAc, 1 L at each concentration),