diethyl 4-oxoheptanedioate

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

Procedure: To a solution of hydrazine monohydrate (95 mmol, 4.76 g) in abs. ethanol (50 mL) was added diethyl 4-oxopimelate (100 mmol, 23.03 g). The mixture was stirred at rt. for 1 h and evaporated to dryness in vacuo to give the desired product (18.96 g, quantitative) as a pure (HPCL 260 nm) white solid. The material was analyzed by HPLC (260 nm) and found to be pure. UV λmax 242 nm. 1H NMR (CDCl3): δ 8.61 (s br, 1H, NH), 4.11 (q, J=7.1 Hz, 2H, CH2), 2.60-2.55 (m, 4H, 2CH2), 2.50.2.40 (m, 4H, 2CH2), 1.22 (t, J=7.1 Hz, 3H, CH3). 13C NMR (CDCl3): δ 172.41, 167.16, 153.35, 60.36, 30.85 29.76, 25.17, 14.00. FAB+ MS: 199.1085 (M+H+, calc. for C9H14N2O3+H+ 199.1083). evaporated to dryness in vacuo

Conditions: temp:77.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To EtOH (27.8 L), triethyl orthoformate (9.26 L, 55.6 mol) and diethyl 4-oxopimelate (5.93 L, 27.8 mol) was added p-toluenesulfonic acid monohydrate (0.053 kg, 0.278 mol), and the reaction mixture was heated to 77.0° C. with stirring for 20 h. Heating was discontinued, and ethanol was removed by distillation under vacuum, starting with the batch at 63° C. The remaining orange ketal solution was dissolved in toluene (32 L) and transferred to a 100-L extractor that had been charged with 2% NaHCO3 (24 L), with stirring. Heating ethanol was removed by distillation under vacuum starting with the batch at 63° C The remaining orange ketal solution was dissolved in toluene (32 L) had been charged with 2% NaHCO3 (24 L) with stirring

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

Procedure: In a three neck flask equipped with a Dean-Stark trap, phenylhydrazine hydrochloride and diethyl 4-oxoheptanedioate (1 equiv.) were combined in toluene (1.15 M). The suspension was stirred 48 h at reflux. The reaction mixture was cooled to rt and concentrated under vacuum to afford the desired material as a brown oil which was used as such in the next step. at reflux concentrated under vacuum

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

Procedure: In a three neck flask equipped with a Dean-Stark trap, phenylhydrazine hydrochloride and diethyl 4-oxoheptanedioate (1 equiv.) were combined in Toluene (1.15 M). The suspension was stirred 48 h at reflux. The reaction mixture was cooled to rt and concentrated under vacuum to afford the desired material as a brown oil which was used as such in the next step. at reflux concentrated under vacuum

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

Procedure: In a three neck flask equipped with a Dean-Stark trap, phenylhydrazine hydrochloride and diethyl 4-oxoheptanedioate (1 equiv.) were combined in Toluene (1.15 M). The suspension was stirred 48 h at reflux. The reaction mixture was cooled to rt and concentrated under vacuum to afford the desired material as a brown oil which was used as such in the next step. at reflux concentrated under vacuum

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

Procedure: A stirred solution of 12.3 g (53.5 mmol) of diethyl 4-oxopimelate, 10.4 g (53.5 mmol) of 2,4-dihydroxy-3-propylacetophenone, and 3.8 g (55 mmol) of pyrrolidine in 62 ml of toluene was refluxed under a water separator. After 4 hours, the mixture was allowed to cool. The solvent was removed under reduced pressure and the resultant oil was chromatographed on silica gel using ethyl acetate-hexane as eluent. The titled diester (4.98 g) was found to be homogeneous by thin-layer chromatography (20% by volume ethyl acetate/hexane on silica gel plates) and was used in subsequent reactions without further purification. to cool The solvent was removed under reduced pressure the resultant oil was chromatographed on silica gel was used in subsequent reactions without further purification

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

Procedure: A stirred solution of 12.3 g (53.5 mmol) of diethyl 4-oxopimelate, 10.4 g (53.5 mmol) of 2,4-dihydroxy-3-propylacetophenone, and 3.8 g (55 mmol) of pyrrolidine in 62 ml of toluene was refluxed under a water separator. After 4 hours, the mixture was allowed to cool. The solvent was removed under reduced pressure and the resultant oil was chromatographed on silica gel using ethyl acetate-hexane as eluent. The titled diester (4.98 g) was found to be homogeneous by thin-layer chromatography (20% by volume ethyl acetate/hexane on silica gel plates) and was used in subsequent reactions without further purification. to cool The solvent was removed under reduced pressure the resultant oil was chromatographed on silica gel was used in subsequent reactions without further purification

Conditions: temp:77.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To EtOH (27.8 L), triethyl orthoformate (9.26 L, 55.6 mol) and diethyl 4-oxopimelate (5.93 L, 27.8 mol) was added p-toluenesulfonic acid monohydrate (0.053 kg, 0.278 mol), and the reaction mixture was heated to 77.0° C. with stirring for 20 h. Heating was discontinued, and ethanol was removed by distillation under vacuum, starting with the batch at 63° C. The remaining orange ketal solution was dissolved in toluene (32 L) and transferred to a 100-L extractor that had been charged with 2% NaHCO3 (24 L), with stirring. Heating ethanol was removed by distillation under vacuum starting with the batch at 63° C The remaining orange ketal solution was dissolved in toluene (32 L) had been charged with 2% NaHCO3 (24 L) with stirring

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

Procedure: The title compound was prepared according to the procedure of Example 1 using 3-mercapto-1,2-propanediol (10.8 g, 0.1 mol), diethyl 4-oxopimelate (23 g, 0.1 mol) and boron trifluoride etherate (2.5 ml) in methylene chloride (300 ml). The crude product was chromatographed on silica gel using 40% ethyl acetate/hexane as eluent to give 14.5 g (45%) of product. The crude product was chromatographed on silica gel using 40% ethyl acetate/hexane as eluent

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

Procedure: A stirred solution of 1,2,3-trimercaptopropane (10.0 g, 0.071 mol) and diethyl 4-oxopimelate (16.43 g, 0.071 mol) in methylene chloride (300 ml) under nitrogen atmosphere was treated with boron trifluoride etherate (2 ml). After stirring for 3 days at room temperature, the reaction was quenched by addition of 200 ml of 5% sodium bicarbonate solution. The organic phase was separated and dried over anhydrous sodium sulfate. The drying agent was filtered and the filtrate concentrated on the rotary evaporator. The residue was chromatographed on silica gel using 5% ethyl acetate/hexane as eluent to give 10 g (40%) of the title compound as an oil. the reaction was quenched by addition of 200 ml of 5% sodium bicarbonate solution The organic phase was separated dried over anhydrous sodium sulfate The drying agent was filtered the filtrate concentrated on the rotary evaporator The residue was chromatographed on silica gel using 5% ethyl acetate/hexane as eluent

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

Procedure: A stirred solution of 12.3 g (53.5 mmol) of diethyl 4-oxopimelate, 10.4 g (53.5 mmol) of 2,4-dihydroxy-3-propylacetophenone, and 3.8 g (55 mmol) of pyrrolidine in 62 ml of toluene was refluxed under a water separator. After 4 hours, the mixture was allowed to cool. The solvent was removed under reduced pressure and the resultant oil was chromatographed on silica gel using ethyl acetate-hexane as eluent. The titled diester (4.98 g) was found to be homogeneous by thin-layer chromatography (20% by volume ethyl acetate/hexane on silica gel plates) and was used in subsequent reactions without further purification. to cool The solvent was removed under reduced pressure the resultant oil was chromatographed on silica gel was used in subsequent reactions without further purification

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

Procedure: The title compound was prepared according to the procedure of Example 1 using 3-mercapto-1,2-propanediol (10.8 g, 0.1 mol), diethyl 4-oxopimelate (23 g, 0.1 mol) and boron trifluoride etherate (2.5 ml) in methylene chloride (300 ml). The crude product was chromatographed on silica gel using 40% ethyl acetate/hexane as eluent to give 14.5 g (45%) of product. The crude product was chromatographed on silica gel using 40% ethyl acetate/hexane as eluent