isocyanomethane

Conditions: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 2-phenoxybenzoyl chloride (1.09 g) and methyl isocyanide (383 mg) was stirred at 50° C. for 3 hours. Then, the mixture was diluted with acetone (10 ml), and water (2 ml) and calcium carbonate (500 mg) were added. The resulting mixture was stirred for 1 hour. The mixture was neutralized with dilute hydrochloric acid and extracted with methylene chloride. After drying the organic layer, the solvent was evaporated under reduced pressure. The residue was subjected to column chromatography on silica gel and eluted with hexane-ethyl acetate (6:1) to obtain the title compound as crystals (1.04 g, Yield: 87.1%), mp: 94°-95° C. were added The resulting mixture was stirred for 1 hour extracted with methylene chloride After drying the organic layer the solvent was evaporated under reduced pressure eluted with hexane-ethyl acetate (6:1)

Conditions: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 2-phenoxybenzoyl chloride (1.09 g) and methyl isocyanide (383 mg) was stirred at 50° C. for 3 hours. Then, the mixture was diluted with acetone (10 ml), and water (2 ml) and calcium carbonate (500 mg) were added. The resulting mixture was stirred for 1 hour. The mixture was neutralized with dilute hydrochloric acid and extracted with methylene chloride. After drying the organic layer, the solvent was evaporated under reduced pressure. The residue was subjected to column chromatography on silica gel and eluted with hexane-ethyl acetate (6:1) to obtain the title compound as crystals (1.04 g, Yield: 87.1%), mp: 94°-95° C. were added The resulting mixture was stirred for 1 hour extracted with methylene chloride After drying the organic layer the solvent was evaporated under reduced pressure eluted with hexane-ethyl acetate (6:1)

Conditions: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Methyl isocyanide (0.84 ml) was added to 2-methylbenzoyl chloride (1.55 g). The mixture was stirred at 60° C. for 16 hours. Then, 5N hydrochloric acid (1.5 ml) and acetone (2 ml) were added, and the mixture was stirred at room temperature for 1.5 hours for hydrolysis. Then, water was added. The mixture was extracted with methylene chloride, washed with water and dried. The solvent was evaporated under reduced pressure to obtain the title compound as an oil (1.68 g). the mixture was stirred at room temperature for 1.5 hours for hydrolysis The mixture was extracted with methylene chloride washed with water dried The solvent was evaporated under reduced pressure

Conditions: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Methyl isocyanide (0.84 ml) was added to 2-methylbenzoyl chloride (1.55 g). The mixture was stirred at 60° C. for 16 hours. Then, 5N hydrochloric acid (1.5 ml) and acetone (2 ml) were added, and the mixture was stirred at room temperature for 1.5 hours for hydrolysis. Then, water was added. The mixture was extracted with methylene chloride, washed with water and dried. The solvent was evaporated under reduced pressure to obtain the title compound as an oil (1.68 g). the mixture was stirred at room temperature for 1.5 hours for hydrolysis The mixture was extracted with methylene chloride washed with water dried The solvent was evaporated under reduced pressure

Conditions: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 2-methylbenzoyl chloride (1.55 g) and methyl isocyanide (492 mg) was stirred at 60° C. for 6 hours. Then, the mixture was diluted with acetone (20 ml), and water (4 ml) and calcium carbonate (1.00 g) were added. The stirring of the resulting mixture was continued for 1 hour. The mixture was neutralized with dilute hydrochloric acid and extracted with methylene chloride. The organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure. The residue was subjected to column chromatography on silica gel and eluted with hexane-ethyl acetate (5:1) to obtain the title compound (1.71 g, Yield: 96.6%). were added The stirring of the resulting mixture was continued for 1 hour extracted with methylene chloride The organic layer was washed with saturated brine dried over anhydrous magnesium sulfate The solvent was evaporated under reduced pressure eluted with hexane-ethyl acetate (5:1)

Conditions: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 2-methylbenzoyl chloride (1.55 g) and methyl isocyanide (492 mg) was stirred at 60° C. for 6 hours. Then, the mixture was diluted with acetone (20 ml), and water (4 ml) and calcium carbonate (1.00 g) were added. The stirring of the resulting mixture was continued for 1 hour. The mixture was neutralized with dilute hydrochloric acid and extracted with methylene chloride. The organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure. The residue was subjected to column chromatography on silica gel and eluted with hexane-ethyl acetate (5:1) to obtain the title compound (1.71 g, Yield: 96.6%). were added The stirring of the resulting mixture was continued for 1 hour extracted with methylene chloride The organic layer was washed with saturated brine dried over anhydrous magnesium sulfate The solvent was evaporated under reduced pressure eluted with hexane-ethyl acetate (5:1)

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Methyl isocyanide (5.04 g., 0.026 mol) was added to (±)-tropan-2-one (2 g., 0.0143 mol) in dimethoxyethane (80 ml) and the solution cooled to 0° C. Ethanol (2 ml) was added followed by addition of potassium tert-butoxide (5.64 g, 6.05 mol). The mixture was then heated at 50° C. for three hours, cooled and poured into a saturated potassium carbonate solution (300 ml). This was extracted with ethyl acetate (3×100 ml) and the combined extracts dried (K2CO3), filtered and evaporated to give a crude oil which was abosorbed on alumina (40 g, grade 1 neutralised by addition of 10% water) from ethereal solution. The solution was eluted with a progressively graded mixture of ether, ethyl acetate and methanol to give 8-methyl-8-azabicyclo[3.2.1]octane-2nitrile (1.1 g--46%) as an oil. The mixture was then heated at 50° C. for three hours cooled This was extracted with ethyl acetate (3×100 ml) the combined extracts dried (K2CO3) filtered evaporated to give a crude oil which The solution was eluted with a progressively graded mixture of ether, ethyl acetate and methanol

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Methyl isocyanide (5.04 g., 0.026 mol) was added to (±)-tropan-2-one (2 g., 0.0143 mol) in dimethoxyethane (80 ml) and the solution cooled to 0° C. Ethanol (2 ml) was added followed by addition of potassium tert-butoxide (5.64 g, 6.05 mol). The mixture was then heated at 50° C. for three hours, cooled and poured into a saturated potassium carbonate solution (300 ml). This was extracted with ethyl acetate (3×100 ml) and the combined extracts dried (K2CO3), filtered and evaporated to give a crude oil which was abosorbed on alumina (40 g, grade 1 neutralised by addition of 10% water) from ethereal solution. The solution was eluted with a progressively graded mixture of ether, ethyl acetate and methanol to give 8-methyl-8-azabicyclo[3.2.1]octane-2nitrile (1.1 g--46%) as an oil. The mixture was then heated at 50° C. for three hours cooled This was extracted with ethyl acetate (3×100 ml) the combined extracts dried (K2CO3) filtered evaporated to give a crude oil which The solution was eluted with a progressively graded mixture of ether, ethyl acetate and methanol

Conditions: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Prepared according to the procedure of Schollkopf (J. Am. Chem. Soc. 112 (10) 4070 (1990)). To a solution of methyl isocyanide (2.88 g, 0.0702 mol) in THF (50 mL) under argon at -78° C. was added dropwise n-butyllithium solution (1.6M in hexanes, 44 mL) over 15 mins. After stirring for an additional 20 mins at -78° C., a solution of ethyl diethoxyacetate (12.62 g, 0.0702 mol) in THF (15 mL) was added dropwise over 20 mins. The bath was allowed to warm to -30° C. over the next 2 hrs and the reaction was then stirred at 0° C. for 30 mins. The reaction was quenched at 0° C. with glacial HOAc (4.22 g, 0.0702 mol) and the solvent was removed by rotary evaporation in vacuo. The golden solid was partitioned with H2O (45 mL) and EtOAc (200 mL), and the aqueous extracted with EtOAc (2×200 mL). The combined organic was washed with satd aq NaCl, dried over Na2SO4, and concentrated in vacuo to a brown oil. Chromatography on a 300 g SiO2 flash column with a gradient of EtOAc/hexane (10%, 15%, 20%) afforded the desired compound as a colorless liquid (7.46 g, 0.0436 mol, 62%): 1H NMR (CDCl3) δ1.25 (t, J=6.9 Hz, 6H), 3.56-3.70 (m, 4H), 5.62 (s, 1H), 7.26 (s, 1H), 7.86 (s, 1H). Mass spectrum: (M+H)+ =172. Prepared to warm to -30° C. over the next 2 hrs the reaction was then stirred at 0° C. for 30 mins the solvent was removed by rotary evaporation in vacuo The golden solid was partitioned with H2O (45 mL) and EtOAc (200 mL) the aqueous extracted with EtOAc (2×200 mL) The combined organic was washed with satd aq NaCl dried over Na2SO4 concentrated in vacuo to a brown oil

Conditions: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Prepared according to the procedure of Schollkopf (J. Am. Chem. Soc. 112 (10) 4070 (1990)). To a solution of methyl isocyanide (2.88 g, 0.0702 mol) in THF (50 mL) under argon at -78° C. was added dropwise n-butyllithium solution (1.6M in hexanes, 44 mL) over 15 mins. After stirring for an additional 20 mins at -78° C., a solution of ethyl diethoxyacetate (12.62 g, 0.0702 mol) in THF (15 mL) was added dropwise over 20 mins. The bath was allowed to warm to -30° C. over the next 2 hrs and the reaction was then stirred at 0° C. for 30 mins. The reaction was quenched at 0° C. with glacial HOAc (4.22 g, 0.0702 mol) and the solvent was removed by rotary evaporation in vacuo. The golden solid was partitioned with H2O (45 mL) and EtOAc (200 mL), and the aqueous extracted with EtOAc (2×200 mL). The combined organic was washed with satd aq NaCl, dried over Na2SO4, and concentrated in vacuo to a brown oil. Chromatography on a 300 g SiO2 flash column with a gradient of EtOAc/hexane (10%, 15%, 20%) afforded the desired compound as a colorless liquid (7.46 g, 0.0436 mol, 62%): 1H NMR (CDCl3) δ 1.25 (t, J=6.9 Hz, 6H), 3.56-3.70 (m, 4H), 5.62 (s, 1H), 7.26 (s, 1H), 7.86 (s, 1H). Mass spectrum: (M+H)+ =172. Prepared to warm to -30° C. over the next 2 hrs the reaction was then stirred at 0° C. for 30 mins the solvent was removed by rotary evaporation in vacuo The golden solid was partitioned with H2O (45 mL) and EtOAc (200 mL) the aqueous extracted with EtOAc (2×200 mL) The combined organic was washed with satd aq NaCl dried over Na2SO4 concentrated in vacuo to a brown oil

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

Procedure: Two moles of a cyclohexane solution of BuLi (1.218 mmol, 1 equiv.) was added to 4 mL of a tetrahydrofuran solution of isocyanomethane (50 mg, 1.218 mmol, 10 equiv.) at a temperature of −78° C. After ten minutes, 0.5 mL of a THF solution of methylpyridine-2-sulfinate (210 mg, 1.34 mmol, 11 equiv.) was added at once. After thirty minutes, 5 mL of saturated, aqueous NH4Cl was added. A crude product was extracted with CH2Cl2 (2×15 mL), dried (NaSO4), and concentrated. The crude product was purified by radial chromatography (1 mm alumina plate, 30:70 ethylacetate/hexanes) to produce 131 mg (65% yield) of 2-((isocyanomethyl)sulfinyl)pyridine as a white solid having M.P. 91-93° C.; IR (film) 542, 776, 960, 992, 1038, 1053, 1427, 1452, 1578, 2139, 2923, 2997 cm−1; 1H NMR: δ 4.73 (ABq, Δv=83.3 Hz, J=14.3 Hz, 2H), 7.49-7.52 (m, 1H), 8.04-8.12 (m, 2H), 8.67-8.68 (m, 1H); 13C NMR: δ 60.33, 125.65, 125.82, 138.56, 150.02, 160.58, 165.10. After ten minutes After thirty minutes A crude product was extracted with CH2Cl2 (2×15 mL) dried (NaSO4) concentrated The crude product was purified by radial chromatography (1 mm alumina plate, 30:70 ethylacetate/hexanes)

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

Procedure: Two moles of a cyclohexane solution of BuLi (1.218 mmol, 1 equiv.) was added to 4 mL of a tetrahydrofuran solution of isocyanomethane (50 mg, 1.218 mmol, 10 equiv.) at a temperature of −78° C. After ten minutes, 0.5 mL of a THF solution of methylpyridine-2-sulfinate (210 mg, 1.34 mmol, 11 equiv.) was added at once. After thirty minutes, 5 mL of saturated, aqueous NH4Cl was added. A crude product was extracted with CH2Cl2 (2×15 mL), dried (NaSO4), and concentrated. The crude product was purified by radial chromatography (1 mm alumina plate, 30:70 ethylacetate/hexanes) to produce 131 mg (65% yield) of 2-((isocyanomethyl)sulfinyl)pyridine as a white solid having M.P. 91-93° C.; IR (film) 542, 776, 960, 992, 1038, 1053, 1427, 1452, 1578, 2139, 2923, 2997 cm−1; 1H NMR: δ 4.73 (ABq, Δv=83.3 Hz, J=14.3 Hz, 2H), 7.49-7.52 (m, 1H), 8.04-8.12 (m, 2H), 8.67-8.68 (m, 1H); 13C NMR: δ 60.33, 125.65, 125.82, 138.56, 150.02, 160.58, 165.10. After ten minutes After thirty minutes A crude product was extracted with CH2Cl2 (2×15 mL) dried (NaSO4) concentrated The crude product was purified by radial chromatography (1 mm alumina plate, 30:70 ethylacetate/hexanes)