diethyl 2-benzylbutanedioate

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

Procedure: The product from step (b) was suspended in acetyl chloride (24 ml) and the suspension refluxed for 3 hours, then evaporated in vacuo to give a white solid which was triturated and washed with 60-80 petrol and dried in vacuo to give the desired product (9.7 g). The 200 MHz 1H NMR was consistent with the proposed structure. the suspension refluxed for 3 hours evaporated in vacuo to give a white solid which was triturated washed with 60-80 petrol dried in vacuo

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

Procedure: A solution of the product from step (a) (23.6 g) in c.HCl (326 ml) was stirred under reflux for 46 hours, then cooled. The resulting precipitate was extracted with chloroform (×3) and the extracts combined, washed with 2M aqu. KOH (×2), acidified to pH 4.0 (2M aqu. HCl) and cooled. The resulting precipitate was filtered off, washed with water and dried in vacuo to give the desired product (15.7 g). The 200 MHz 1H NMR was consistent with the proposed structure. under reflux for 46 hours cooled The resulting precipitate was extracted with chloroform (×3) washed with 2M aqu cooled The resulting precipitate was filtered off washed with water dried in vacuo

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

Procedure: A solution of the product from step (a) (23.6 g) in c.HCl (326 ml) was stirred under reflux for 46 hours, then cooled. The resulting precipitate was extracted with chloroform (×3) and the extracts combined, washed with 2M aqu. KOH (×2), acidified to pH 4.0 (2M aqu. HCl) and cooled. The resulting precipitate was filtered off, washed with water and dried in vacuo to give the desired product (15.7 g). The 200 MHz 1H NMR was consistent with the proposed structure. under reflux for 46 hours cooled The resulting precipitate was extracted with chloroform (×3) washed with 2M aqu cooled The resulting precipitate was filtered off washed with water dried in vacuo

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

Procedure: To a suspension of NaH (2.2 g, 54 mmole) in THF (200 mL) was added diethyl 2-(phenylmethyl)butanedioate (12.5 g, 49.9 mmole). After 30 min at RT, bromomethyl phthalimide was added to the reaction mixture and the contents were stirred for 14 h at RT. The reaction was quenched with H2O (15 mL), diluted with Et2O (300 mL) and layers separated. The organic layer was concentrated under vacuum and the resulting residue recrystallized from EtOH)(0°) to give the title compound (13 g, 64%) as a white solid: LCMS (ES) m/z 410 (M+H)+. The reaction was quenched with H2O (15 mL) diluted with Et2O (300 mL) and layers separated The organic layer was concentrated under vacuum the resulting residue recrystallized from EtOH)(0°)

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

Procedure: To a suspension of NaH (2.2 g, 54 mmole) in THF (200 mL) was added diethyl 2-(phenylmethyl)butanedioate (12.5 g, 49.9 mmole). After 30 min at RT, bromomethyl phthalimide was added to the reaction mixture and the contents were stirred for 14 h at RT. The reaction was quenched with H2O (15 mL), diluted with Et2O (300 mL) and layers separated. The organic layer was concentrated under vacuum and the resulting residue recrystallized from EtOH (0°) to give the title compound (13 g, 64%) as a white solid: The reaction was quenched with H2O (15 mL) diluted with Et2O (300 mL) and layers separated The organic layer was concentrated under vacuum the resulting residue recrystallized from EtOH (0°)

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

Procedure: The product from step (b) was suspended in acetyl chloride (24 ml) and the suspension refluxed for 3 hours, then evaporated in vacuo to give a white solid which was triturated and washed with 60-80 petrol and dried in vacuo to give the desired product (9.7 g). The 200 MHz 1H NMR was consistent with the proposed structure. the suspension refluxed for 3 hours evaporated in vacuo to give a white solid which was triturated washed with 60-80 petrol dried in vacuo

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

Procedure: A solution of the product from step (a) (23.6 g) in c.HCl (326 ml) was stirred under reflux for 46 hours, then cooled. The resulting precipitate was extracted with chloroform (×3) and the extracts combined, washed with 2M aqu. KOH (×2), acidified to pH 4.0 (2M aqu. HCl) and cooled. The resulting precipitate was filtered off, washed with water and dried in vacuo to give the desired product (15.7 g). The 200 MHz 1H NMR was consistent with the proposed structure. under reflux for 46 hours cooled The resulting precipitate was extracted with chloroform (×3) washed with 2M aqu cooled The resulting precipitate was filtered off washed with water dried in vacuo