2-trimethylsilylethanesulfonyl chloride

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: To a solution of 1H-indole-5-carboxylic acid methyl ester (3.6 g, 20.6 mmol) in tetrahydrofuran (180 mL) at 0° C., was added sodium hydride (0.65 g, 21.9 mmol). After 10 min., 2-trimethylsilanylethanesulfonyl chloride (4.4 g, 21.9 mmol) was added and the reaction mixture was allowed to warm to room temperature. After 3 h, acetic acid (1.6 mL, 26.8 mmol) was added and the reaction mixture was concentrated. The crude product was chromatographed (Biotage 40M column, 2.5% ethyl acetate-hexanes) to afford 1-(2-trimethylsilanylethanesulfonyl)-indole-5-carboxylic acid methyl ester (5.43 g) as a white solid. After 3 h the reaction mixture was concentrated The crude product was chromatographed (Biotage 40M column, 2.5% ethyl acetate-hexanes)

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

Procedure: Sodium hydride (96 mg, 4.07 mmol) was added to a solution of N-tert-butoxycarbonyl-4-(5-fluoroindol-3-yl)piperidine (1.28 g, 4.07 mmol), [prepared as described in Step 1, above] in DMF (6 ml) at 0° C. and the reaction mixture was stirred for 30 min. 2-Trimethylsilylethanesulfonyl chloride (820 mg, 4.07 mmol) was added and the reaction mixture was slowly warmed to RT over 30 min. After 2.5 h, the reaction mixture was quenched with water (10 ml) and the product was extracted into methylene chloride. The combined organic layers were dried over MgSO4 and concentrated in vacuo. Due to incomplete reaction the above steps were repeated on the isolated crude reaction mixture. The final residue was chromatographed (PTLC, SiO2, 20% ethyl acetate/hexanes) to afford N-tert-butoxycarbonyl-4-[5-fluoro-1-(2-trimethylsilylethanesulfonyl)indol-3-yl]piperidine (84%) as a clear oil. After 2.5 h the reaction mixture was quenched with water (10 ml) the product was extracted into methylene chloride The combined organic layers were dried over MgSO4 concentrated in vacuo Due to incomplete reaction the above steps isolated crude reaction mixture The final residue was chromatographed (PTLC, SiO2, 20% ethyl acetate/hexanes)

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

Procedure: A solution of 2,2-dimethyl-4-aminomethyl-1,3-dioxolane (10.0 g, 0.08 mol) and triethylamine (8.1 g, 11.1 mL, 0.08 mol) in 100 mL of N,N-dimethylformamide is cooled to 0 C. under argon atmosphere. Then β-trimethylsilylethanesulfonyl chloride (16.0 g, 0.08 mol) is added dropwise. The solution is allowed to reach 25 C. and is stirred for 15 hours. The solvents are removed under reduced pressure and the crude residue is partitioned between dichloromethane (100 mL) and 5% sodium bicarbonate solution (50 mL). The layers are separated and the organic layer is dried over anhydrous sodium sulfate and evaporated to give 2,2-dimethyl-4-[N-(β-trimethylsilylethanesulfonyl)-aminomethyl]-1,3-dioxolane. The solvents are removed under reduced pressure the crude residue is partitioned between dichloromethane (100 mL) and 5% sodium bicarbonate solution (50 mL) The layers are separated the organic layer is dried over anhydrous sodium sulfate evaporated

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

Procedure: A solution of 2,2-dimethyl-4-aminomethyl-1,3-dioxolane (10.0 g, 0.08 mol) and triethylamine (8.1 g, 11.1 mL, 0.08 mol) in 100 mL of N,N-dimethylformamide is cooled to 0 C. under argon atmosphere. Then β-trimethylsilylethanesulfonyl chloride (16.0 g, 0.08 mol) is added dropwise. The solution is allowed to reach 25 C. and is stirred for 15 hours. The solvents are removed under reduced pressure and the crude residue is partitioned between dichloromethane (100 mL) and 5% sodium bicarbonate solution (50 mL). The layers are separated and the organic layer is dried over anhydrous sodium sulfate and evaporated to give 2,2-dimethyl-4-[N-(β-trimethylsilylethanesulfonyl)-aminomethyl]-1,3-dioxolane. The solvents are removed under reduced pressure the crude residue is partitioned between dichloromethane (100 mL) and 5% sodium bicarbonate solution (50 mL) The layers are separated the organic layer is dried over anhydrous sodium sulfate evaporated

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

Procedure: Sodium hydride (96 mg, 4.07 mmol) was added to a solution of N-tert-butoxycarbonyl-4-(5-fluoroindol-3-yl)piperidine (1.28 g, 4.07 mmol), [prepared as described in Step 1, above] in DMF (6 ml) at 0° C. and the reaction mixture was stirred for 30 min. 2-Trimethylsilylethanesulfonyl chloride (820 mg, 4.07 mmol) was added and the reaction mixture was slowly warmed to RT over 30 min. After 2.5 h, the reaction mixture was quenched with water (10 ml) and the product was extracted into methylene chloride. The combined organic layers were dried over MgSO4 and concentrated in vacuo. Due to incomplete reaction the above steps were repeated on the isolated crude reaction mixture. The final residue was chromatographed (PTLC, SiO2, 20% ethyl acetate/hexanes) to afford N-tert-butoxycarbonyl-4-[5-fluoro-1-(2-trimethylsilylethanesulfonyl)indol-3-yl]piperidine (84%) as a clear oil. After 2.5 h the reaction mixture was quenched with water (10 ml) the product was extracted into methylene chloride The combined organic layers were dried over MgSO4 concentrated in vacuo Due to incomplete reaction the above steps isolated crude reaction mixture The final residue was chromatographed (PTLC, SiO2, 20% ethyl acetate/hexanes)