5-[(4-fluorophenyl)methyl]-2,2-dimethyl-1,3-dioxane-4,6-dione

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

Procedure: The title compound was prepared by substituting 5-(4-chlorobenzyl)-2,2-dimethyl-1,3-dioxane-4,6-dione (Intermediate 3: step a) with 5-(4-fluorobenzyl)-2,2-dimethyl-1,3-dioxane-4,6-dione (Intermediate 4: step a) then following the procedure described for the preparation of 2-(4-chlorobenzyl)malonic acid (Intermediate 3: step b).

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

Procedure: The title compound was prepared by substituting 5-(4-chlorobenzyl)-2,2-dimethyl-1,3-dioxane-4,6-dione (Intermediate 3: step a) with 5-(4-fluorobenzyl)-2,2-dimethyl-1,3-dioxane-4,6-dione (Intermediate 4: step a) then following the procedure described for the preparation of 2-(4-chlorobenzyl)malonic acid (Intermediate 3: step b).

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

Procedure: The title compound was prepared using 4-fluorobenzaldehyde in place of 4-chlorobenzaldehyde using the procedure described for the preparation of 5-(4-chlorobenzyl)-2,2-dimethyl-1,3-dioxane-4,6-dione (Intermediate 3: step a).

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

Procedure: The title compound was prepared by substituting 5-(benzo[b]thiophen-2-ylmethyl)-2,2-dimethyl-1,3-dioxane-4,6-dione (Intermediate 39: step a) with 5-(4-fluorobenzyl)-2,2-dimethyl-1,3-dioxane-4,6-dione (Intermediate 42: step a) then following the procedure described for the preparation of 2-(benzo[b]thiophen-2-ylmethyl)malonic acid (Intermediate 39: step b).

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

Procedure: The title compound was prepared using 4-fluorobenzaldehyde in place of benzo[b]thiophene-2-carbaldehyde using the procedure described for the preparation of 5-(benzo[b]thiophen-2-ylmethyl)-2,2-dimethyl-1,3-dioxane-4,6-dione (Intermediate 39: step a).

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

Procedure: The title compound was prepared using 4-fluorobenzaldehyde in place of benzo[b]thiophene-2-carbaldehyde using the procedure described for the preparation of 5-(benzo[b]thiophen-2-ylmethyl)-2,2-dimethyl-1,3-dioxane-4,6-dione (Intermediate 39: step a).

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

Procedure: A solution of 5-(4-fluorobenzyl)-2,2-dimethyl-1,3-dioxane-4,6-dione (34.118 g, 135.26 mmol, Intermediate 7: step a) and 6 M aqueous NaOH (136 mL) was heated to 120° C. under a reflux condenser and positive pressure of nitrogen for two days. The mixture was allowed to cool to room temperature, water and ethyl acetate were added, and the layers were separated. The aqueous layer was acidified to pH 0 with 6 M aqueous HCl and the mixture was stirred at room temperature for 30 minutes. Dichloromethane was added to the mixture, the organic layer was separated, and the aqueous layer was extracted with excess ethyl acetate. The combined organic layers were dried (Na2SO4), filtered, and concentrated to dryness to provide the title compound. the layers were separated Dichloromethane was added to the mixture the organic layer was separated the aqueous layer was extracted with excess ethyl acetate The combined organic layers were dried (Na2SO4) filtered concentrated to dryness

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

Procedure: Proline (5.748 g, 49.42 mmol) was added to a solution of 4-fluorobenzaldehyde (24.99 g, 197.3 mmol) and Meldrum's acid (29.01 g, 197.3 mmol) in EtOH (900 mL). The mixture was stirred at room temperature for 1.5 hours, then diethyl 1,4-dihydro-2,6-dimethyl-3,5-pyridinedicarboxylate (50.99 g, 197.3 mmol) was added along with an additional 100 mL of EtOH. The mixture was stirred overnight and EtOH was removed under reduced pressure. The residue was triturated with i-PrOH and filtered to provide the title compound as a white solid. The mixture was stirred overnight EtOH was removed under reduced pressure The residue was triturated with i-PrOH filtered

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

Procedure: The title compound was prepared by substituting 5-(4-chlorobenzyl)-2,2-dimethyl-1,3-dioxane-4,6-dione (Intermediate 3: step a) with 5-(4-fluorobenzyl)-2,2-dimethyl-1,3-dioxane-4,6-dione (Intermediate 4: step a) then following the procedure described for the preparation of 2-(4-chlorobenzyl)malonic acid (Intermediate 3: step b).

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

Procedure: The title compound was prepared using 4-fluorobenzaldehyde in place of 4-chlorobenzaldehyde using the procedure described for the preparation of 5-(4-chlorobenzyl)-2,2-dimethyl-1,3-dioxane-4,6-dione (Intermediate 3: step a).

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

Procedure: The title compound was prepared by substituting 5-(benzo[b]thiophen-2-ylmethyl)-2,2-dimethyl-1,3-dioxane-4,6-dione (Intermediate 39: step a) with 5-(4-fluorobenzyl)-2,2-dimethyl-1,3-dioxane-4,6-dione (Intermediate 42: step a) then following the procedure described for the preparation of 2-(benzo[b]thiophen-2-ylmethyl)malonic acid (Intermediate 39: step b).

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

Procedure: The title compound was prepared using 4-fluorobenzaldehyde in place of benzo[b]thiophene-2-carbaldehyde using the procedure described for the preparation of 5-(benzo[b]thiophen-2-ylmethyl)-2,2-dimethyl-1,3-dioxane-4,6-dione (Intermediate 39: step a).