(1E)-2-fluoro-N-hydroxybenzenecarboximidoyl 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:; See reaction.notes.procedure_details.

Procedure: To a solution (0° C., N2) of 2-fluorobenzoylchloride oxime (0.50 g, 2.9 mmol) and methyl-2-butynoate (0.57 g, 5.8 mmol) in Et2O (15 ml) was added a solution of Et3N (0.52 ml) in Et2O (2 ml) over a period of 1 h followed by warming to room temperature while stirring overnight (17 h). The reaction was diluted with Et2O, washed (H2O then brine), dried (MgSO4), filtered, and concentrated. Column chromatography (silica gel, hexanes/EtOAc gradient) gave the title compound (0.39 g, 58%). washed (H2O brine), dried (MgSO4) filtered concentrated

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

Procedure: To a solution (0° C., N2) of 2-fluorobenzoylchloride oxime (0.50 g, 2.9 mmol) and methyl-2-butynoate (0.57 g, 5.8 mmol) in Et2O (15 ml) was added a solution of Et3N (0.52 ml) in Et2O (2 ml) over a period of 1 h followed by warming to room temperature while stirring overnight (17 h). The reaction was diluted with Et2O, washed (H2O then brine), dried (MgSO4), filtered, and concentrated. Column chromatography (silica gel, hexanes/EtOAc gradient) gave the title compound (0.39 g, 58%). washed (H2O brine), dried (MgSO4) filtered concentrated

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

Procedure: In a similar manner as described in Preparation Example 17, by using methanol (160 mL), 2-fluoro-N-hydroxybenzimidoyl chloride (8.00 g, 46.09 mmol), methylcyanoacetate (5.94 g, 59.92 mmol) and sodium methoxide (4.98 g, 92.18 mmol), a white solid required compound (8.23 g, 34.82 mmol, 76%) was obtained. In a similar manner as described in Preparation Example 17

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

Procedure: In a similar manner as described in Preparation Example 17, by using methanol (160 mL), 2-fluoro-N-hydroxybenzimidoyl chloride (8.00 g, 46.09 mmol), methylacetoacetate (10.07 g, 92.18 mmol) and sodium methoxide (7.47 g, 138.27 mmol), a white solid required compound (7.84 g, 33.33 mmol, 72%) was obtained. In a similar manner as described in Preparation Example 17

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

Procedure: In a similar manner as described in Preparation Example 17, by using methanol (160 mL), 2-fluoro-N-hydroxybenzimidoyl chloride (8.00 g, 46.09 mmol), methylacetoacetate (10.07 g, 92.18 mmol) and sodium methoxide (7.47 g, 138.27 mmol), a white solid required compound (7.84 g, 33.33 mmol, 72%) was obtained. In a similar manner as described in Preparation Example 17

Conditions: temp:-10.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: In 1 liter dichloromethane was dissolved 55.0 g 2-fluorobenzaldehyde oxime at room temperature with stirring. The resulting solution was cooled to -10° C. and Cl2 was bubbled in at such a rate to maintain the temperature below 15° C. After a dark blue color was generated (2-3 minutes) a solution of triethylamine (50 ml) in dichloromethane (100 ml) was added dropwise concurrently with Cl2 addition. When the reaction mixture had maintained a yellow color, additions of the triethylamine solution and Cl2 were discontinued. Concentration of the reaction mixture left an oil which was dissolved in ether and washed four times with 3N HCl followed by a final wash with brine. The organic layer was dried (MgSO4), filtered and concentrated in vacuo to give 60.0 g of 2-fluoro-N-hydroxybenzenecarboximidoyl chloride as an oil which solidified on standing. Cl2 was bubbled in at such a rate to maintain the temperature below 15° C (2-3 minutes) was added dropwise concurrently with Cl2 addition When the reaction mixture had maintained a yellow color, additions of the triethylamine solution and Cl2 Concentration of the reaction mixture left an oil which was dissolved in ether washed four times with 3N HCl a final wash with brine The organic layer was dried (MgSO4) filtered concentrated in vacuo

Conditions: temp:-10.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: In 1 liter dichloromethane was dissolved 55.0 g 2-fluorobenzaldehyde oxime at room temperature with stirring. The resulting solution was cooled to -10° C. and Cl2 was bubbled in at such a rate to maintain the temperature below 15° C. After a dark blue color was generated (2-3 minutes) a solution of triethylamine (50 ml) in dichloromethane (100 ml) was added dropwise concurrently with Cl2 addition. When the reaction mixture had maintained a yellow color, additions of the triethylamine solution and Cl2 were discontinued. Concentration of the reaction mixture left an oil which was dissolved in ether and washed four times with 3N HCl followed by a final wash with brine. The organic layer was dried (MgSO4), filtered and concentrated in vacuo to give 60.0 g of 2-fluoro-N-hydroxybenzenecarboximidoyl chloride as an oil which solidified on standing. Cl2 was bubbled in at such a rate to maintain the temperature below 15° C (2-3 minutes) was added dropwise concurrently with Cl2 addition When the reaction mixture had maintained a yellow color, additions of the triethylamine solution and Cl2 Concentration of the reaction mixture left an oil which was dissolved in ether washed four times with 3N HCl a final wash with brine The organic layer was dried (MgSO4) filtered concentrated in vacuo

Conditions: temp:-10.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: In 1 liter dichloromethane was dissolved 55.0 g 2-fluorobenzaldehyde oxime at room temperature with stirring. The resulting solution was cooled to -10° C. and Cl2 was bubbled in at such a rate to maintain temperature below 15° C. After a dark blue color was generated (2-3 minutes) a solution of triethylamine (50 ml) in dichloromethane (100 ml) was added dropwise concurrently with Cl2 addition. When the reaction mixture had maintained a yellow color, additions of the triethylamine solution and Cl2 were discontinued. Concentration of the reaction mixture left an oil which was dissolved in ether and washed four times with 3N HCl followed by a final wash with brine. The organic layer was dried (MgSO4), filtered and concentrated in vacuo to give 60.0 g of 2-fluoro-N-hydroxybenzenecarboximidoyl chloride as an oil which solidified on standing. Cl2 was bubbled in at such a rate to maintain temperature below 15° C (2-3 minutes) was added dropwise concurrently with Cl2 addition When the reaction mixture had maintained a yellow color, additions of the triethylamine solution and Cl2 Concentration of the reaction mixture left an oil which was dissolved in ether washed four times with 3N HCl a final wash with brine The organic layer was dried (MgSO4) filtered concentrated in vacuo

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

Procedure: To a solution (0° C., N2) of 2-fluorobenzoylchloride oxime (0.50 g, 2.9 mmol) and methyl-2-butynoate (0.57 g, 5.8 mmol) in Et2O (15 ml) was added a solution of Et3N (0.52 ml) in Et2O (2 ml) over a period of 1 h followed by warming to room temperature while stirring overnight (17 h). The reaction was diluted with Et2O, washed (H2O then brine), dried (MgSO4), filtered, and concentrated. Column chromatography (silica gel, hexanes/EtOAc gradient) gave the title compound (0.39 g, 58%). washed (H2O brine), dried (MgSO4) filtered concentrated