1-(chloromethyl)-4-methylsulfanylbenzene

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

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

Procedure: 4-Methylmercaptobenzyl chloride (160 g, 0.94 mol) was added dropwise, under nitrogen, with stirring to 183 g (1.1 mole) of triethylphosphite which was heated at reflux. When the addition of the 4-methylmercaptobenzyl chloride was completed, the mixture was refluxed for additional 4 hours. The product was distilled in vacuo to yield 229 g (89%) of water clear, viscous liquid bp 142°-145° C. (0.025 mm). was heated at reflux the mixture was refluxed for additional 4 hours The product was distilled in vacuo

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

Procedure: To a stirred solution of 154 g (1 mol) of 4-methylmercaptobenzyl alcohol in 1 liter of dry benzene was added dropwise 80 mL 1.1 mol) of thionyl chloride. The mixture immediately turned blue. After the addition of the thionyl chloride was completed, the mixture was heated at reflux for 2 hours. After cooling the benzene and excess thionyl chloride were distilled at ambient pressure. The product was distilled in vacuo at 105° C. (0.5 mm), to yield 160 g (93%) of water clear liquid. the mixture was heated at reflux for 2 hours were distilled at ambient pressure The product was distilled in vacuo at 105° C. (0.5 mm) to yield 160 g (93%) of water clear liquid

Conditions: temp:82.51; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Under an atmosphere of nitrogen, 25.9 g (150 mmol) of 4-(methylthio)benzyl chloride were dissolved in 45.5 g of toluene. 9.29 g (180 mmol) of sodium cyanide, 0.92 g (2.9 mmol) of tetrabutylammonium chloride and 14.4 g of water were then added. The mixture was stirred at 80-85° C. for 2 h. The reaction mixture was admixed with 30 g of toluene and 45 g of water, the aqueous phase was decanted off and the organic phase was concentrated. This gave a residue of 24.6 g of the title product in a yield of >95% (according to NMR) in the form of a pink solid. the aqueous phase was decanted off the organic phase was concentrated

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of 4-methylthiobenzyl chloride (3.1 g) and triphenylphosphine (4.72 g) was heated in toluene (35 mL) at reflux for 18 hr. The mixture was cooled to 0° C. and filtered. The resulting solid was used as such in the next step. at reflux for 18 hr filtered

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

Procedure: To a cooled solution (−70° C.) of LDA (1 M) in THF (37 mL) was added dropwise a solution of 2-methyl-1-indanone (J.A.C.S. Vol. 98, 8119-8124 (1976)) (2.5 g, 17 mmol) in THF (20 mL). The resulting dark red solution was stirred at room temperature for 3 hours, then cooled to −20° C. and a solution for 4-methylthiobenzyl chloride (3.1 g, 18 mmol) in THF (15 mL) was added slowly. The addition completed, the reaction mixture was stirred at −20° C. for 30 minutes before being quenched with 3N aqueous HCl (50 mL) and brine (50 mL). The product was extracted with ether, dried over MgSO4 and evaporated to dryness. The oily residue was chromatographed on silica gel eluting with a 1:5 mixture of ethyl acetate-hexane to afford the pure title compound as an oil. cooled to −20° C. The addition the reaction mixture was stirred at −20° C. for 30 minutes before being quenched with 3N aqueous HCl (50 mL) and brine (50 mL) The product was extracted with ether dried over MgSO4 evaporated to dryness The oily residue was chromatographed on silica gel eluting with a 1:5 mixture of ethyl acetate-hexane