2-(2-methylsulfanylphenyl)acetonitrile

Conditions: temp:20.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 3.05 g of (2-methylsulfanylphenyl)acetonitrile were added dropwise to a mixture of 3.3 ml of 30% strength sodium methylate solution in MOH and 10 ml of dry THF and stirred for 1 h at 20° C. 1.69 ml of methyl acrylate were then added at 20° C. and the reaction mixture was heated for 4 h under reflux. After cooling, the reaction mixture was poured onto cold 2 N hydrochloric acid and extracted three times with 100 ml each of DCM. The combined organic phases were washed with 100 ml of water and 100 ml of sodium chloride solution, dried with magnesium sulfate and concentrated in vacuo. The residue (4.7 g) was dissolved in 10 ml of dimethyl sulfoxide, 1.5 g of sodium chloride were added and the mixture was heated for 5 h at 180° C. After cooling, 150 ml of EA were added and the mixture was washed three times with 100 ml each of water. The organic phase was dried with magnesium sulfate and concentrated in vacuo. The residue was purified by preparative HPLC (acetonitrile/water). 1.2 g of the title compound were obtained. the reaction mixture was heated for 4 h under reflux After cooling extracted three times with 100 ml each of DCM The combined organic phases were washed with 100 ml of water and 100 ml of sodium chloride solution dried with magnesium sulfate concentrated in vacuo The residue (4.7 g) was dissolved in 10 ml of dimethyl sulfoxide 1.5 g of sodium chloride were added the mixture was heated for 5 h at 180° C After cooling 150 ml of EA were added the mixture was washed three times with 100 ml each of water The organic phase was dried with magnesium sulfate concentrated in vacuo The residue was purified by preparative HPLC (acetonitrile/water)

Conditions: temp:20.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 3.05 g of (2-methylsulfanylphenyl)acetonitrile were added dropwise to a mixture of 3.3 ml of 30% strength sodium methylate solution in MOH and 10 ml of dry THF and stirred for 1 h at 20° C. 1.69 ml of methyl acrylate were then added at 20° C. and the reaction mixture was heated for 4 h under reflux. After cooling, the reaction mixture was poured onto cold 2 N hydrochloric acid and extracted three times with 100 ml each of DCM. The combined organic phases were washed with 100 ml of water and 100 ml of sodium chloride solution, dried with magnesium sulfate and concentrated in vacuo. The residue (4.7 g) was dissolved in 10 ml of dimethyl sulfoxide, 1.5 g of sodium chloride were added and the mixture was heated for 5 h at 180° C. After cooling, 150 ml of EA were added and the mixture was washed three times with 100 ml each of water. The organic phase was dried with magnesium sulfate and concentrated in vacuo. The residue was purified by preparative HPLC (acetonitrile/water). 1.2 g of the title compound were obtained. the reaction mixture was heated for 4 h under reflux After cooling extracted three times with 100 ml each of DCM The combined organic phases were washed with 100 ml of water and 100 ml of sodium chloride solution dried with magnesium sulfate concentrated in vacuo The residue (4.7 g) was dissolved in 10 ml of dimethyl sulfoxide 1.5 g of sodium chloride were added the mixture was heated for 5 h at 180° C After cooling 150 ml of EA were added the mixture was washed three times with 100 ml each of water The organic phase was dried with magnesium sulfate concentrated in vacuo The residue was purified by preparative HPLC (acetonitrile/water)

Conditions: temp:40.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Phosphorus tribromide (75 g) in toluene (50 ml) was added to a stirred mixture of 2-methylthiobenzyl alcohol (42.5 g) in toluene (25 ml) over 10 minutes at 5° C. The mixture was then stirred at 40° C. for 1 hour, water (100 ml) was added and stirring continued at ambient temperature for 1 hour. The organic layer was separated and the aqueous layer extracted with ethyl acetate. The combined organic layers yielded an oil. The oil (58.6 g) was dissolved in a 1:2 mixture of water and ethanol and sodium cyanide (26.5 g) was added over 15 minutes. The mixture was stirred at 50° C. for 1.5 hours then poured onto water (500 ml) and extracted with ethyl acetate. The extract yielded 2-methylthiophenylacetonitrile. stirring continued at ambient temperature for 1 hour The organic layer was separated the aqueous layer extracted with ethyl acetate The combined organic layers yielded an oil was added over 15 minutes The mixture was stirred at 50° C. for 1.5 hours then poured onto water (500 ml) extracted with ethyl acetate

Conditions: temp:20.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 3.05 g of (2-methylsulfanylphenyl)acetonitrile were added dropwise to a mixture of 3.3 ml of 30% strength sodium methylate solution in MOH and 10 ml of dry THF and stirred for 1 h at 20° C. 1.69 ml of methyl acrylate were then added at 20° C. and the reaction mixture was heated for 4 h under reflux. After cooling, the reaction mixture was poured onto cold 2 N hydrochloric acid and extracted three times with 100 ml each of DCM. The combined organic phases were washed with 100 ml of water and 100 ml of sodium chloride solution, dried with magnesium sulfate and concentrated in vacuo. The residue (4.7 g) was dissolved in 10 ml of dimethyl sulfoxide, 1.5 g of sodium chloride were added and the mixture was heated for 5 h at 180° C. After cooling, 150 ml of EA were added and the mixture was washed three times with 100 ml each of water. The organic phase was dried with magnesium sulfate and concentrated in vacuo. The residue was purified by preparative HPLC (acetonitrile/water). 1.2 g of the title compound were obtained. the reaction mixture was heated for 4 h under reflux After cooling extracted three times with 100 ml each of DCM The combined organic phases were washed with 100 ml of water and 100 ml of sodium chloride solution dried with magnesium sulfate concentrated in vacuo The residue (4.7 g) was dissolved in 10 ml of dimethyl sulfoxide 1.5 g of sodium chloride were added the mixture was heated for 5 h at 180° C After cooling 150 ml of EA were added the mixture was washed three times with 100 ml each of water The organic phase was dried with magnesium sulfate concentrated in vacuo The residue was purified by preparative HPLC (acetonitrile/water)

Conditions: temp:40.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Phosphorus tribromide (75 g) in toluene (50 ml) was added to a stirred mixture of 2-methylthiobenzyl alcohol (42.5 g) in toluene (25 ml) over 10 minutes at 5° C. The mixture was then stirred at 40° C. for 1 hour, water (100 ml) was added and stirring continued at ambient temperature for 1 hour. The organic layer was separated and the aqueous layer extracted with ethyl acetate. The combined organic layers yielded an oil. The oil (58.6 g) was dissolved in a 1:2 mixture of water and ethanol and sodium cyanide (26.5 g) was added over 15 minutes. The mixture was stirred at 50° C. for 1.5 hours then poured onto water (500 ml) and extracted with ethyl acetate. The extract yielded 2-methylthiophenylacetonitrile. stirring continued at ambient temperature for 1 hour The organic layer was separated the aqueous layer extracted with ethyl acetate The combined organic layers yielded an oil was added over 15 minutes The mixture was stirred at 50° C. for 1.5 hours then poured onto water (500 ml) extracted with ethyl acetate