trimethyl-(4-oxidofuro[3,2-b]pyridin-4-ium-2-yl)silane

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

Conditions: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 2-(Trimethylsilyl)furo[3,2-b]pyridine N-oxide (10.51 g, 50.7 mmol) dissolved in POCl3 (47.3 ml, 507 mmol) in a sealed flask and heated at 100° C. for one hour. The reaction was cooled to RT, poured into a beaker washing with minimal DCM, and cooled in a brine bath. Saturated sodium bicarbonate solution was added very slowly and then solid sodium bicarbonate was added portion wise until the solution was at about pH=8. The solution was extracted twice with DCM, and the combined organic layers were dried with sodium sulfate, filtered, and concentrated. The material was purified via column chromatography (gradient elution 5-40% EtOAc:Hex) to afford 7-chloro-2-(trimethylsilyl)furo[3,2-b]pyridine as a pale yellow oil. MS: M+H+=226.2 The reaction was cooled to RT poured into a beaker washing with minimal DCM cooled in a brine bath Saturated sodium bicarbonate solution was added very slowly solid sodium bicarbonate was added portion wise until the solution The solution was extracted twice with DCM the combined organic layers were dried with sodium sulfate filtered concentrated The material was purified via column chromatography (gradient elution 5-40% EtOAc:Hex)

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

Procedure: 2-(Trimethylsilyl)furo[3,2-b]pyridine (14.68 g, 76.7 mmol) was dissolved in 80 mL DCM and cooled to 0° C. m-CPBA (33.1 g, 192 mmol) was dissolved in 160 mL DCM and slowly added to the reaction vessel. Upon complete addition, the reaction was warmed to RT and stirred for three hours. Reaction was diluted with DCM and washed twice with saturated sodium bicarbonate solution. 30 g of carbonate scavenger beads (˜30 mmol) were added to the organic layer and the solution was stirred for 30 minutes. The reaction was filtered, washed with brine, dried with sodium sulfate, filtered, and concentrated. The material was purified via column chromatography (gradient elution 0-10% MeOH:DCM) to afford 2-(trimethylsilyl)furo[3,2-b]pyridine N-oxide as a light brown oil that solidified under high vacuum. MS: M+H+=208.2 slowly added to the reaction vessel Upon complete addition Reaction washed twice with saturated sodium bicarbonate solution 30 g of carbonate scavenger beads (˜30 mmol) were added to the organic layer the solution was stirred for 30 minutes The reaction was filtered washed with brine dried with sodium sulfate filtered concentrated The material was purified via column chromatography (gradient elution 0-10% MeOH:DCM)

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

Procedure: 2-(Trimethylsilyl)furo[3,2-b]pyridine (14.68 g, 76.7 mmol) was dissolved in 80 mL DCM and cooled to 0° C. m-CPBA (33.1 g, 192 mmol) was dissolved in 160 mL DCM and slowly added to the reaction vessel. Upon complete addition, the reaction was warmed to RT and stirred for three hours. Reaction was diluted with DCM and washed twice with saturated sodium bicarbonate solution. 30 g of carbonate scavenger beads (˜30 mmol) were added to the organic layer and the solution was stirred for 30 minutes. The reaction was filtered, washed with brine, dried with sodium sulfate, filtered, and concentrated. The material was purified via column chromatography (gradient elution 0-10% MeOH:DCM) to afford 2-(trimethylsilyl)furo[3,2-b]pyridine N-oxide as a light brown oil that solidified under high vacuum. MS: M+H+=208.2 slowly added to the reaction vessel Upon complete addition Reaction washed twice with saturated sodium bicarbonate solution 30 g of carbonate scavenger beads (˜30 mmol) were added to the organic layer the solution was stirred for 30 minutes The reaction was filtered washed with brine dried with sodium sulfate filtered concentrated The material was purified via column chromatography (gradient elution 0-10% MeOH:DCM)

Conditions: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 2-(Trimethylsilyl)furo[3,2-b]pyridine N-oxide (10.51 g, 50.7 mmol) dissolved in POCl3 (47.3 ml, 507 mmol) in a sealed flask and heated at 100° C. for one hour. The reaction was cooled to RT, poured into a beaker washing with minimal DCM, and cooled in a brine bath. Saturated sodium bicarbonate solution was added very slowly and then solid sodium bicarbonate was added portion wise until the solution was at about pH=8. The solution was extracted twice with DCM, and the combined organic layers were dried with sodium sulfate, filtered, and concentrated. The material was purified via column chromatography (gradient elution 5-40% EtOAc:Hex) to afford 7-chloro-2-(trimethylsilyl)furo[3,2-b]pyridine as a pale yellow oil. MS: M+H+=226.2 The reaction was cooled to RT poured into a beaker washing with minimal DCM cooled in a brine bath Saturated sodium bicarbonate solution was added very slowly solid sodium bicarbonate was added portion wise until the solution The solution was extracted twice with DCM the combined organic layers were dried with sodium sulfate filtered concentrated The material was purified via column chromatography (gradient elution 5-40% EtOAc:Hex)

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

Procedure: 2-(Trimethylsilyl)furo[3,2-b]pyridine (14.68 g, 76.7 mmol) was dissolved in 80 mL DCM and cooled to 0° C. m-CPBA (33.1 g, 192 mmol) was dissolved in 160 mL DCM and slowly added to the reaction vessel. Upon complete addition, the reaction was warmed to RT and stirred for three hours. Reaction was diluted with DCM and washed twice with saturated sodium bicarbonate solution. 30 g of carbonate scavenger beads (—30 mmol) were added to the organic layer and the solution was stirred for 30 minutes. The reaction was filtered, washed with brine, dried with sodium sulfate, filtered, and concentrated. The material was purified via column chromatography (gradient elution 0-10% MeOH:DCM) to afford 2-(trimethylsilyl)furo[3,2-b]pyridine N-oxide as a light brown oil that solidified under high vacuum. MS: M+H+=208.2 slowly added to the reaction vessel Upon complete addition Reaction washed twice with saturated sodium bicarbonate solution 30 g of carbonate scavenger beads (—30 mmol) were added to the organic layer the solution was stirred for 30 minutes The reaction was filtered washed with brine dried with sodium sulfate filtered concentrated The material was purified via column chromatography (gradient elution 0-10% MeOH:DCM)

Conditions: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 2-(Trimethylsilyl)furo[3,2-b]pyridine N-oxide (10.51 g, 50.7 mmol) dissolved in POCl3 (47.3 ml, 507 mmol) in a sealed flask and heated at 100° C. for one hour. The reaction was cooled to RT, poured into a beaker washing with minimal DCM, and cooled in a brine bath. Saturated sodium bicarbonate solution was added very slowly and then solid sodium bicarbonate was added portion wise until the solution was at about pH=8. The solution was extracted twice with DCM, and the combined organic layers were dried with sodium sulfate, filtered, and concentrated. The material was purified via column chromatography (gradient elution 5-40% EtOAc:Hex) to afford 7-chloro-2-(trimethylsilyl)furo[3,2-b]pyridine as a pale yellow oil. MS: M+H+=226.2 The reaction was cooled to RT poured into a beaker washing with minimal DCM cooled in a brine bath Saturated sodium bicarbonate solution was added very slowly solid sodium bicarbonate was added portion wise until the solution The solution was extracted twice with DCM the combined organic layers were dried with sodium sulfate filtered concentrated The material was purified via column chromatography (gradient elution 5-40% EtOAc:Hex)

Conditions: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 2-(Trimethylsilyl)furo[3,2-b]pyridine N-oxide (10.51 g, 50.7 mmol) dissolved in POCl3 (47.3 ml, 507 mmol) in a sealed flask and heated at 100° C. for one hour. The reaction was cooled to RT, poured into a beaker washing with minimal DCM, and cooled in a brine bath. Saturated sodium bicarbonate solution was added very slowly and then solid sodium bicarbonate was added portion wise until the solution was at about pH=8. The solution was extracted twice with DCM, and the combined organic layers were dried with sodium sulfate, filtered, and concentrated. The material was purified via column chromatography (gradient elution 5-40% EtOAc:Hex) to afford 7-chloro-2-(trimethylsilyl)furo[3,2-b]pyridine as a pale yellow oil. MS: M+H+=226.2 The reaction was cooled to RT poured into a beaker washing with minimal DCM cooled in a brine bath Saturated sodium bicarbonate solution was added very slowly solid sodium bicarbonate was added portion wise until the solution The solution was extracted twice with DCM the combined organic layers were dried with sodium sulfate filtered concentrated The material was purified via column chromatography (gradient elution 5-40% EtOAc:Hex)

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

Procedure: 2-(Trimethylsilyl)furo[3,2-b]pyridine (14.68 g, 76.7 mmol) was dissolved in 80 mL DCM and cooled to 0° C. m-CPBA (33.1 g, 192 mmol) was dissolved in 160 mL DCM and slowly added to the reaction vessel. Upon complete addition, the reaction was warmed to RT and stirred for three hours. Reaction was diluted with DCM and washed twice with saturated sodium bicarbonate solution. 30 g of carbonate scavenger beads (—30 mmol) were added to the organic layer and the solution was stirred for 30 minutes. The reaction was filtered, washed with brine, dried with sodium sulfate, filtered, and concentrated. The material was purified via column chromatography (gradient elution 0-10% MeOH:DCM) to afford 2-(trimethylsilyl)furo[3,2-b]pyridine N-oxide as a light brown oil that solidified under high vacuum. MS: M+H+=208.2 slowly added to the reaction vessel Upon complete addition Reaction washed twice with saturated sodium bicarbonate solution 30 g of carbonate scavenger beads (—30 mmol) were added to the organic layer the solution was stirred for 30 minutes The reaction was filtered washed with brine dried with sodium sulfate filtered concentrated The material was purified via column chromatography (gradient elution 0-10% MeOH:DCM)

Conditions: temp:2.51; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 2-Trimethylsilanyl-furo[3,2-b]pyridine (268 g, 0.14 mol) is dissolved in dichloromethane (3 l) and stirred at 0-5° C. To the solution is added 3-chloroperbenzoic acid over 30 min, stirred 1 h and warmed up to room temperature. After 14 h the reaction mixture is extracted with NaHCO3 solution and water. The organic layer is separated and dried over Na2SO4. The drying agent is filtered and the solvent is removed in vacuum; yield: 296 g 2-trimethylsilanyl-furo[3,2-b]pyridine 4-oxide; HPLC/MS: 2.0 min, [M+H]=208; stirred 1 h warmed up to room temperature After 14 h the reaction mixture is extracted with NaHCO3 solution and water The organic layer is separated dried over Na2SO4 The drying agent is filtered the solvent is removed in vacuum 2.0 min, [M+H]=208

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

Procedure: A solution of 2-(trimethylsilyl)furo(3,2-b)pyridine N-oxide (32 g, 0.153 mol) in POCl3 (150 ml) is heated to 100° C. for 2 h in a sealed pressure tube. The reaction mixture is cooled to RT, concentrated under vacuum, the residue is dissolved in DCM (500 ml), washed with saturated sodium bicarbonate (100 ml×2), water (50 ml×2) and with sat brine (50 ml), dried over sodium sulphate and concentrated under vacuum. The crude material is purified by column chromatography by using petrolether/ethyl acetate (9:1) as an eluent to afford the title compound as (18 g, 52%) light brown oil. TLC: hexane/ethyl acetate: (8/2): Rf=0.80; 1H NMR (DMSO-d6, 400 MHz) δ [ppm] 8.461-8.448 (1H, d, J=5.2 Hz), 7.502-7.477 (2H, m), 0.372-0.355 (9H, s); LCMS (method C): 3.29 min (purity 95.8%), M+H+ 226.0. concentrated under vacuum the residue is dissolved in DCM (500 ml) washed with saturated sodium bicarbonate (100 ml×2), water (50 ml×2) and with sat brine (50 ml) dried over sodium sulphate concentrated under vacuum The crude material is purified by column chromatography

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

Procedure: A solution of m-CPBA (17 g, 0.098 mmol) in DCM (80 ml) is added to a solution of 2-(Trimethylsilyl)furo(3,2-b)pyridine (7.5 g, 0.0392 mol) in dry DCM (50 ml) at 0° C. The reaction mixture is stirred at RT for 4 h and then diluted with DCM (100 ml), washed with saturated sodium bicarbonate (2×100 ml) and saturated brine (50 ml), dried over sodium sulphate and evaporated to afford the title compound as (6 g, 73.5%) light brown oil. TLC: chloroform/methanol (9/1): Rf=0.8; 1H NMR (DMSO-d6, 400 MHz) δ [ppm] 8.21-8.19 (1H, d, J1=6.4 Hz), 7.693-7.671 (1H, d, J1=8.52 Hz), 7.465-7.163 (1H, d, J1=1 Hz), 7.333-7.296 (1H, dd, J1=6.36 Hz, J2=8.48 Hz), 0.372-0.355 (9H, s). washed with saturated sodium bicarbonate (2×100 ml) and saturated brine (50 ml) dried over sodium sulphate evaporated