methyl 2-fluorobenzoate

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: Methyl 2-fluorobenzoate (27) (25 g, 160 mmol) was dissolved in ethanol (200 mL) and hydrazine monohydrate (11.8 mL, 240 mmol) was added. The mixture was heated to reflux for 4 hr then allowed to cool to room temperature overnight. The reaction was incomplete. After heating for a further 2 hr, starting material still remained. Additional hydrazine monohydrate (4 mL) was added. After heating for 2-3 hr the reaction was nearly complete. The mixture was cooled and concentrated under reduced pressure. Water (50 mL) was added to the residue and the aqueous layer was saturated with solid NaCl. The product was extracted with EtOAc (3×100 mL). The combined organic solution was dried over Na2SO4, filtered, and concentrated under reduced pressure. The residue was triturated with heptane (100 mL), filtered, and dried to provide 23.8 g (95%) of 13 as a pinkish solid. The mixture was heated to reflux for 4 hr After heating for a further 2 hr After heating for 2-3 hr the reaction The mixture was cooled concentrated under reduced pressure Water (50 mL) was added to the residue The product was extracted with EtOAc (3×100 mL) The combined organic solution was dried over Na2SO4 filtered concentrated under reduced pressure The residue was triturated with heptane (100 mL) filtered dried

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

Procedure: Methyl 2-fluorobenzoate (27) (25 g, 160 mmol) was dissolved in ethanol (200 mL) and hydrazine monohydrate (11.8 mL, 240 mmol) was added. The mixture was heated to reflux for 4 hr then allowed to cool to room temperature overnight. The reaction was incomplete. After heating for a further 2 hr, starting material still remained. Additional hydrazine monohydrate (4 mL) was added. After heating for 2-3 hr the reaction was nearly complete. The mixture was cooled and concentrated under reduced pressure. Water (50 mL) was added to the residue and the aqueous layer was saturated with solid NaCl. The product was extracted with EtOAc (3×100 mL). The combined organic solution was dried over Na2SO4, filtered, and concentrated under reduced pressure. The residue was triturated with heptane (100 mL), filtered, and dried to provide 23.8 g (95%) of 13 as a pinkish solid. The mixture was heated to reflux for 4 hr After heating for a further 2 hr After heating for 2-3 hr the reaction The mixture was cooled concentrated under reduced pressure Water (50 mL) was added to the residue The product was extracted with EtOAc (3×100 mL) The combined organic solution was dried over Na2SO4 filtered concentrated under reduced pressure The residue was triturated with heptane (100 mL) filtered dried

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

Procedure: A mixture of methyl 2-fluorobenzoate (16.0 g, 103.8 mmol) and 4-piperidone propylene ketal (9.8 g, 62.3 mmol) was stirred at room temperature (8 d). Flash chromatography on silica gel (10% MeOH-90% CHCl3) afforded the title compound (44).

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

Procedure: A mixture of methyl 2-fluorobenzoate (16.0 g, 103.8 mmol) and 4-piperidone propylene ketal (9.8 g, 62.3 mmol) was stirred at room temperature (8 d). Flash chromatography on silica gel (10% MeOH-90% CHCl3) afforded the title compound (44).

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

Procedure: Using benzyl nipecotate (5.90 g, 26.9 mmol) and methyl 2-fluorobenzoate (3.70 mL, 29.0 mmol), the same procedure was followed as in Step 1c of Example 1 to give 1.64 g (17%) of the desired compound as a colorless oil.