ethyl 2-methylsulfanylacetate

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: In analogous fashion, 4-trifluoromethylaniline was reacted with t-butyl hypochlorite, ethyl 2-(methylthio)acetate and triethylamine followed by reduction of the 3-thiomethyl-5-trifluoromethyl-2-oxindole thus obtained with Raney nickel, to give 5-trifluoromethyl-2-oxindole, m.p. 189.5°-190.5° C.

反応条件: temp:-60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Ethyl (methylsulphanyl)acetate (27.31 mmoles) is added dropwise to a solution of the compound obtained in Step E (23.75 mmoles) in THF (200 ml) at −60° C. under a nitrogen atmosphere. tBuOCl (27.31 mmoles) is added dropwise to the reaction mixture over 20 minutes, keeping the temperature between −60° C. and −55° C. After stirring for 3 hours at −60° C., triethylamine (29.68 mmoles) is added dropwise. The reaction mixture is brought to ambient temperature; aqueous 3M HCl solution (340 ml) is then added and stirring is carried out for a further 2 hours. The organic phase is evaporated and the aqueous suspension is extracted with DCM. The organic phases are combined, then washed with 2M HCl solution and then with saturated NaCl solution, dried over sodium sulphate, filtered and evaporated to dryness. The residue is triturated in ethyl ether, filtered and dried in vacuo to yield the title product, which is used directly in the next Step. the temperature between −60° C. and −55° C is brought to ambient temperature stirring is carried out for a further 2 hours The organic phase is evaporated the aqueous suspension is extracted with DCM washed with 2M HCl solution with saturated NaCl solution, dried over sodium sulphate filtered evaporated to dryness The residue is triturated in ethyl ether filtered dried in vacuo

反応条件: temp:-60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Ethyl (methylsulphanyl)acetate (27.31 mmoles) is added dropwise to a solution of the compound obtained in Step E (23.75 mmoles) in THF (200 ml) at −60° C. under a nitrogen atmosphere. tBuOCl (27.31 mmoles) is added dropwise to the reaction mixture over 20 minutes, keeping the temperature between −60° C. and −55° C. After stirring for 3 hours at −60° C., triethylamine (29.68 mmoles) is added dropwise. The reaction mixture is brought to ambient temperature; aqueous 3M HCl solution (340 ml) is then added and stirring is carried out for a further 2 hours. The organic phase is evaporated and the aqueous suspension is extracted with DCM. The organic phases are combined, then washed with 2M HCl solution and then with saturated NaCl solution, dried over sodium sulphate, filtered and evaporated to dryness. The residue is triturated in ethyl ether, filtered and dried in vacuo to yield the title product, which is used directly in the next Step. the temperature between −60° C. and −55° C is brought to ambient temperature stirring is carried out for a further 2 hours The organic phase is evaporated the aqueous suspension is extracted with DCM washed with 2M HCl solution with saturated NaCl solution, dried over sodium sulphate filtered evaporated to dryness The residue is triturated in ethyl ether filtered dried in vacuo

反応条件: temp:-60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of the compound obtained in Step C (38.27 mmoles), in a mixture of CH3CN (115 ml) and THF (115 ml) at −60° C., ethyl (methylsulphanyl)acetate (45.92 mmoles) is added dropwise under a nitrogen atmosphere. tBuOCl (45.92 mmoles) is added dropwise to the reaction mixture over 20 minutes, keeping the temperature between −60° C. and −55° C. After stirring for 1 hour at −60° C., triethylamine (51.66 mmoles) is added dropwise. The reaction mixture is brought to ambient temperature. 240 ml of DCM and then aqueous 3M HCl solution (340 ml) are added. After stiffing for 12 hours at ambient temperature, the reaction mixture is made alkaline (pH 10-11) using 20% aqueous sodium hydroxide solution. After extraction with DCM, the organic phase is washed with saturated aqueous NaCl solution. The organic phase is dried over sodium sulphate, filtered and evaporated to dryness. The product obtained is triturated in ethyl ether, filtered and dried in vacuo to yield the title product which is used directly in the next Step. the temperature between −60° C. and −55° C is brought to ambient temperature After stiffing for 12 hours at ambient temperature After extraction with DCM the organic phase is washed with saturated aqueous NaCl solution The organic phase is dried over sodium sulphate filtered evaporated to dryness The product obtained is triturated in ethyl ether filtered dried in vacuo

反応条件: temp:-60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of the compound obtained in Step C (38.27 mmoles), in a mixture of CH3CN (115 ml) and THF (115 ml) at −60° C., ethyl (methylsulphanyl)acetate (45.92 mmoles) is added dropwise under a nitrogen atmosphere. tBuOCl (45.92 mmoles) is added dropwise to the reaction mixture over 20 minutes, keeping the temperature between −60° C. and −55° C. After stirring for 1 hour at −60° C., triethylamine (51.66 mmoles) is added dropwise. The reaction mixture is brought to ambient temperature. 240 ml of DCM and then aqueous 3M HCl solution (340 ml) are added. After stiffing for 12 hours at ambient temperature, the reaction mixture is made alkaline (pH 10-11) using 20% aqueous sodium hydroxide solution. After extraction with DCM, the organic phase is washed with saturated aqueous NaCl solution. The organic phase is dried over sodium sulphate, filtered and evaporated to dryness. The product obtained is triturated in ethyl ether, filtered and dried in vacuo to yield the title product which is used directly in the next Step. the temperature between −60° C. and −55° C is brought to ambient temperature After stiffing for 12 hours at ambient temperature After extraction with DCM the organic phase is washed with saturated aqueous NaCl solution The organic phase is dried over sodium sulphate filtered evaporated to dryness The product obtained is triturated in ethyl ether filtered dried in vacuo

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of 4-amino-benzonitrile (84.64 mmoles) in DCM (200 ml) under a nitrogen atmosphere, at −78° C., there is added, dropwise, tBuOCl (84.64 mmoles) dissolved in 20 ml of DCM and then, after 10 minutes, ethyl (methylsulphanyl)acetate (84.64 mmoles) dissolved in 20 ml of DCM is added dropwise to the reaction mixture. After stiffing for one hour at −78° C., triethylamine (0.152 mol) is added dropwise. The reaction mixture is stirred at ambient temperature for one hour. Water is added and the phases are then separated. The organic phase is washed with water and then with saturated aqueous NaCl solution. The organic phase is dried over sodium sulphate, filtered and evaporated to dryness. The residue is taken up in ethyl ether and aq. 2M HCl solution is added. After stiffing overnight, the yellow precipitate is filtered off and dried in vacuo to yield the title product, which is used directly in the next reaction. is added dropwise to the reaction mixture After stiffing for one hour at −78° C. the phases are then separated The organic phase is washed with water The organic phase is dried over sodium sulphate filtered evaporated to dryness aq. 2M HCl solution is added After stiffing overnight the yellow precipitate is filtered off dried in vacuo

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of 4-amino-benzonitrile (84.64 mmoles) in DCM (200 ml) under a nitrogen atmosphere, at −78° C., there is added, dropwise, tBuOCl (84.64 mmoles) dissolved in 20 ml of DCM and then, after 10 minutes, ethyl (methylsulphanyl)acetate (84.64 mmoles) dissolved in 20 ml of DCM is added dropwise to the reaction mixture. After stiffing for one hour at −78° C., triethylamine (0.152 mol) is added dropwise. The reaction mixture is stirred at ambient temperature for one hour. Water is added and the phases are then separated. The organic phase is washed with water and then with saturated aqueous NaCl solution. The organic phase is dried over sodium sulphate, filtered and evaporated to dryness. The residue is taken up in ethyl ether and aq. 2M HCl solution is added. After stiffing overnight, the yellow precipitate is filtered off and dried in vacuo to yield the title product, which is used directly in the next reaction. is added dropwise to the reaction mixture After stiffing for one hour at −78° C. the phases are then separated The organic phase is washed with water The organic phase is dried over sodium sulphate filtered evaporated to dryness aq. 2M HCl solution is added After stiffing overnight the yellow precipitate is filtered off dried in vacuo

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of the compound obtained in Step B (0.113 mol) in a mixture of CH3CN (200 ml) and THF (200 ml) at −60° C. there is added, dropwise, ethyl (methylsulphanyl)-acetate (0.136 mol) under a nitrogen atmosphere. tBuOCl (0.136 mol) is added dropwise to the reaction mixture over 20 minutes, keeping the temperature between −60° C. and −55° C. After stiffing for one hour at −50° C., triethylamine (0.152 mol) is added dropwise. The reaction mixture is brought to 0° C. and then aqueous 3M HCl solution (580 ml) is added dropwise. After stiffing for 12 hours at ambient temperature, the organic phases are evaporated in vacuo and then the aqueous phase is extracted with DCM and the organic phases are combined. The organic phase obtained is washed with water and then with saturated aqueous NaCl solution. The organic phase is dried over sodium sulphate, filtered and evaporated to dryness. The product obtained is recrystallised from a mixture of ethyl ether/ethanol. The crystals obtained are filtered off, washed with ether and dried in vacuo at 40° C. to yield the title product, which is used directly in the next Step. there is added the temperature between −60° C. and −55° C is brought to 0° C. After stiffing for 12 hours at ambient temperature the organic phases are evaporated in vacuo the aqueous phase is extracted with DCM The organic phase obtained is washed with water The organic phase is dried over sodium sulphate filtered evaporated to dryness The product obtained is recrystallised from a mixture of ethyl ether/ethanol The crystals obtained are filtered off washed with ether dried in vacuo at 40° C.

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of the compound obtained in Step B (0.113 mol) in a mixture of CH3CN (200 ml) and THF (200 ml) at −60° C. there is added, dropwise, ethyl (methylsulphanyl)-acetate (0.136 mol) under a nitrogen atmosphere. tBuOCl (0.136 mol) is added dropwise to the reaction mixture over 20 minutes, keeping the temperature between −60° C. and −55° C. After stiffing for one hour at −50° C., triethylamine (0.152 mol) is added dropwise. The reaction mixture is brought to 0° C. and then aqueous 3M HCl solution (580 ml) is added dropwise. After stiffing for 12 hours at ambient temperature, the organic phases are evaporated in vacuo and then the aqueous phase is extracted with DCM and the organic phases are combined. The organic phase obtained is washed with water and then with saturated aqueous NaCl solution. The organic phase is dried over sodium sulphate, filtered and evaporated to dryness. The product obtained is recrystallised from a mixture of ethyl ether/ethanol. The crystals obtained are filtered off, washed with ether and dried in vacuo at 40° C. to yield the title product, which is used directly in the next Step. there is added the temperature between −60° C. and −55° C is brought to 0° C. After stiffing for 12 hours at ambient temperature the organic phases are evaporated in vacuo the aqueous phase is extracted with DCM The organic phase obtained is washed with water The organic phase is dried over sodium sulphate filtered evaporated to dryness The product obtained is recrystallised from a mixture of ethyl ether/ethanol The crystals obtained are filtered off washed with ether dried in vacuo at 40° C.

反応条件: temp:-50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of ethyl 4-amino-benzoate (40.0 g) in DCM (900 ml) at −60° C. there is added, dropwise, ethyl (methylsulphanyl)acetate (34.5 ml) under a nitrogen atmosphere. 29.0 g of tBuOCl are then added, dropwise, to the reaction mixture over 25 minutes, maintaining the temperature between −60° C. and −55° C. After stirring for one hour at −50° C., triethylamine (15.4 ml) is added dropwise. The reaction mixture is brought to 0° C. and then aqueous 3M HCl solution (485 ml) is added dropwise. After stirring for 12 hours at ambient temperature, the phases are separated and the organic phase is washed successively with aq. 2M HCl solution, water and then sat. aqueous NaCl solution. The organic phase is dried over sodium sulphate, filtered and evaporated to dryness. The residue obtained is taken up in ether. The crystals obtained are filtered off, washed with ether and dried in vacuo to yield the title product, which is used directly in the next Step. maintaining the temperature between −60° C. and −55° C is brought to 0° C. After stirring for 12 hours at ambient temperature the phases are separated the organic phase is washed successively with aq. 2M HCl solution, water The organic phase is dried over sodium sulphate filtered evaporated to dryness The residue obtained The crystals obtained are filtered off washed with ether dried in vacuo

反応条件: temp:-50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of ethyl 4-amino-benzoate (40.0 g) in DCM (900 ml) at −60° C. there is added, dropwise, ethyl (methylsulphanyl)acetate (34.5 ml) under a nitrogen atmosphere. 29.0 g of tBuOCl are then added, dropwise, to the reaction mixture over 25 minutes, maintaining the temperature between −60° C. and −55° C. After stirring for one hour at −50° C., triethylamine (15.4 ml) is added dropwise. The reaction mixture is brought to 0° C. and then aqueous 3M HCl solution (485 ml) is added dropwise. After stirring for 12 hours at ambient temperature, the phases are separated and the organic phase is washed successively with aq. 2M HCl solution, water and then sat. aqueous NaCl solution. The organic phase is dried over sodium sulphate, filtered and evaporated to dryness. The residue obtained is taken up in ether. The crystals obtained are filtered off, washed with ether and dried in vacuo to yield the title product, which is used directly in the next Step. maintaining the temperature between −60° C. and −55° C is brought to 0° C. After stirring for 12 hours at ambient temperature the phases are separated the organic phase is washed successively with aq. 2M HCl solution, water The organic phase is dried over sodium sulphate filtered evaporated to dryness The residue obtained The crystals obtained are filtered off washed with ether dried in vacuo