Ethyl chloro(methylthio)acetate

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: Tin(IV)chloride (6.67 mL of a 1 M solution in dichloromethane, 6.67 mmol) was added to N-[2-(3-bromophenyl)ethyl]benzenesulfonamide (1.08 g, 3.17 mmol) and ethyl chloro(methylthio)acetate (1.07 g, 6.35 mmol) in 1,2-dichloroethane (11 mL) under argon and the reaction was heated at reflux for 3 hours. After cooling, the mixture was poured into ice water and extracted with ethyl acetate. The organic layer was washed with saturated sodium bicarbonate and brine, dried over anhydrous magnesium sulfate, then filtered and concentrated. The residue was purified by silica gel chromatography eluting with 1:4 ethyl acetate:hexanes to give 1.07 g (79%) of ethyl 6-bromo-2-(phenylsulfonyl)-1,2,3,4-tetrahydro-1-isoquinolinecarboxylate and 255.6 mg (19%) of ethyl 8-bromo-2-(phenylsulfonyl)-1,2,3,4-tetrahydro-1-isoquinolinecarboxylate as oils. the reaction was heated at reflux for 3 hours After cooling extracted with ethyl acetate The organic layer was washed with saturated sodium bicarbonate and brine dried over anhydrous magnesium sulfate filtered concentrated The residue was purified by silica gel chromatography eluting with 1:4 ethyl acetate

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

Procedure: N-Chlorosuccinimide (5.97 g, 44.71 mmol) was added portionwise to ethyl (methylthio)acetate (6.00 g, 44.71 mmol) in carbon tetrachloride (30 mL) at 0° C. under argon and the reaction was allowed to warm to room temperature and stirred for 17 hours. The reaction mixture was filtered and the filtrate was concentrated under vacuum. The oil was purified by distillation to give 3.22 g (43%) of ethyl chloro(methylthio)acetate as an oil. 1H NMR (400 MHz, d6-DMSO): δ 6.10 (s, 1H), 4.20 (q, J=7 Hz, 2H), 2.24 (s, 3H), 1.22 (t, J=7 Hz, 3H). The reaction mixture was filtered the filtrate was concentrated under vacuum The oil was purified by distillation

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

Procedure: In a similar procedure to Stage 2, Step 1 of Example 5, 3-iodo-8-methyl-quinolin-6-ol, was reacted with chloro-methylsulfanyl-acetic acid ethyl ester to give (3-iodo-8-methyl quinolin-6-yloxy)-methylsulfanyl-acetic acid ethyl ester as a yellow coloured solid (MH+ 418).

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

Procedure: In a similar procedure to Stage 2, Step 1 of Example 5, 3-iodo-8-methyl-quinolin-6-ol, was reacted with chloro-methylsulfanyl-acetic acid ethyl ester to give (3-iodo-8-methyl quinolin-6-yloxy)-methylsulfanyl-acetic acid ethyl ester as a yellow coloured solid (MH+ 418).

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

Procedure: In a similar procedure to Stage 2, Step 1 of Example 5, 3-bromo-8-fluoro-quinolin-6-ol was reacted with chloro-methylsulfanyl-acetic acid ethyl ester to give (3-Bromo-8-fluoro-quinolin-6-yloxy)-methylsulfanyl-acetic acid ethyl ester.

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

Procedure: In a similar procedure to Stage 2, Step 1 of Example 5, 3-iodo-6-hydroxy-quinoline was reacted with chloro-methylsulfanyl-acetic acid ethyl ester to give (3-iodo-quinolin-6-yloxy)-methylsulfanyl-acetic acid ethyl ester as a yellow coloured solid.

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

Procedure: To a Stirred Solution of ethyl (methylthio)acetate (10.8 ml) in dichloromethane (300 ml) cooled to −15° C. is added dropwise sulphuryl chloride (8.1 ml). The mixture is allowed to warm to room temperature over two hours and then concentrated under reduced pressure to give crude chloro-methylsulfanyl-acetic acid ethyl ester as a colourless liquid. The product is used in the next step without further purification. 1H NMR (CDCl3) δ ppm: 5.35 (1H, s); 4.25 (2H, m); 2.30 (3H, s); 1.30 (3H, t). concentrated under reduced pressure

Conditions: temp:110.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 16.1 g (50.0 mmol) of [2-[(4-chlorophenyl)sulfonylaminomethyl)indan and 9.27 g (55.0 mmol) of ethyl alpha-chloro-alpha-(methylthio)acetate were dissolved in 50 ml of methylene chloride, to which 6.44 ml (55.0 mmol) of stannic chloride was slowly added dropwise. After stirring for 3 hours, the reaction mixture was poured into ice-water, and the organic phase was collected, washed, dried and condensed. The residue was dissolved in 180 ml of acetic acid, added with 40 g of zinc powder and heated at 110° C. for 1 hour. After cooling, the precipitates were filtrated and washed thoroughly with chloroform and the solvent was removed. The residue was dissolved in 300 ml of ethyl acetate, and washed with water, saturated aqueous sodium bicarbonate solution and water in this order, and dried. The solvent was distilled off under reduced pressure, and the residue was recrystallized from a solvent mixture of ethyl acetate and hexane to obtain 16.7 g of colorless needles. Yield: 82%. was slowly added dropwise the organic phase was collected washed dried condensed After cooling the precipitates were filtrated washed thoroughly with chloroform the solvent was removed The residue was dissolved in 300 ml of ethyl acetate washed with water, saturated aqueous sodium bicarbonate solution and water in this order dried The solvent was distilled off under reduced pressure the residue was recrystallized from a solvent mixture of ethyl acetate and hexane

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