methyl 6,6-dimethoxyhexanoate

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

Procedure: 56 g (0.4 Mole) of cyclohexanone enolacetate in 500 ml of methanol was ozonised in a dry ice-acetone bath until the solution turned blue. 60 ml of dimethyl sulphide was added, and the cooling bath was removed. The temperature rose slowly to 48°, and after it had returned to room temperature, 40 ml of trimethyl orthoformate and 1 ml of acetyl chloride were added. The mixture was then left for 48 h at room temperature. Three identical batches were combined and the solvant was removed in vacuo. The residue was dissolved in ether, washed with brine containing a small amount of NaHCO3, dried (Na2SO4), and distilled to give 193 g of product, b.p. 56°-69°/0.1 Torr. The NMR spectrum indicated the presence of ca. 20% of methyl 6-oxohexanoate. The product was mixed with 100 ml of trimethyl orthoformate, 20 ml of methanol, and 0.5 g of p-toluene sulfonic acid. The mixture was left for 48 h at room temperature, then worked up as above yielding 201 g (88%) of methyl 6,6-dimethoxyhexanoate. b.p. 61°/0.1 Torr.

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

Procedure: After the reaction, MeOH was recovered, following by the same treatment as above to give 9.47 g. of crude 6,6-dimethoxycaproic acid methyl ester. Then, a 10 wt.% aqueous hydrochloric acid solution was added to this crude product, followed by stirring for 6 hours at room temperature. The reaction mixture was treated by usual method to give crude products. Pure 3.20 g. of 5-carbomethoxy-1-pentanal was obtained by column chromatography. was recovered to give 9.47 g The reaction mixture was treated by usual method to give crude products

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

Procedure: 56 g (0.4 Mole) of cyclohexanone enolacetate in 500 ml of methanol was ozonised in a dry ice-acetone bath until the solution turned blue. 60 ml of dimethyl sulphide was added, and the cooling bath was removed. The temperature rose slowly to 48°, and after it had returned to room temperature, 40 ml of trimethyl orthoformate and 1 ml of acetyl chloride were added. The mixture was then left for 48 h at room temperature. Three identical batches were combined and the solvant was removed in vacuo. The residue was dissolved in ether, washed with brine containing a small amount of NaHCO3, dried (Na2SO4), and distilled to give 193 g of product, b.p. 56°-69°/0.1 Torr. The NMR spectrum indicated the presence of ca. 20% of methyl 6-oxohexanoate. The product was mixed with 100 ml of trimethyl orthoformate, 20 ml of methanol, and 0.5 g of p-toluene sulfonic acid. The mixture was left for 48 h at room temperature, then worked up as above yielding 201 g (88%) of methyl 6,6-dimethoxyhexanoate. b.p. 61°/0.1 Torr.

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

Procedure: After the reaction, MeOH was recovered, following by the same treatment as above to give 9.47 g. of crude 6,6-dimethoxycaproic acid methyl ester. Then, a 10 wt.% aqueous hydrochloric acid solution was added to this crude product, followed by stirring for 6 hours at room temperature. The reaction mixture was treated by usual method to give crude products. Pure 3.20 g. of 5-carbomethoxy-1-pentanal was obtained by column chromatography. was recovered to give 9.47 g The reaction mixture was treated by usual method to give crude products

Conditions: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Phosgene (50 mmol of a 20% w/w solution in toluene) was added to N,N-dimethylformamide (3.9 mL, 50 mmol) with stirring in an ice bath over 5 min to give a white paste. This mixture was allowed to stand until no further gas evolution was observed (˜30 min). Methyl 7,7-dimethoxyheptanoate (5.1 g, 25 mmol), prepared from cycloheptene following a published method (Claus, R. E., and Schreiber, S. L. (1986) Ozonolytic cleavage of cyclohexene to terminally differentiated products: methyl 6-oxohexanoate, 6,6-dimethoxyhexanal, methyl 6,6-dimethoxyhexanoate. Organic Syntheses 64, 150-156.), was then added dropwise to the reaction solution followed by heating at 70° C. for 1 hour. After cooling, the solvent was removed by rotary evaporation giving a yellow-brown oil. The oil was suspended in water (20 mL) then 5 mL of 10% aqueous HCl and aniline hydrochloride (6.5 g, 50 mmol) were added. The resulting mixture was sealed in a thick-walled glass pressure tube and heated at 120° C. in an oil bath for 1.5 hours. After heating, the reaction solution was cooled slowly to room temperature over 2 hours, during which the product crystallized (if the reaction is cooled too quickly, a sticky precipitate is formed instead). After filtration and washing with water, 1 is obtained as a yellow solid (2.05 g, 23%). 1H NMR (400 MHz, DMSO-d6): δ 8.72 (d, 2H, J=12 Hz), 7.58 (d, 4H, J=8.4 Hz), 7.51 (t, 4H, J=8.0 Hz), 7.30 (t, 4H, J=7.2 Hz), 2.77 (t, 2H, J=6.4 Hz), 2.27 (t, 2H, J=7.6 Hz), 1.71-1.64 (m, 2H), 1.50-1.42 (m, 2H). HRMS-ESI [M]+ m/z calcd. for [C20H23N2O2]+ 323.1754, found 323.1743. to give a white paste (˜30 min) ), was then added dropwise to the reaction solution After cooling the solvent was removed by rotary evaporation giving a yellow-brown oil The resulting mixture was sealed in a thick-walled glass pressure tube heated at 120° C. in an oil bath for 1.5 hours After heating the reaction solution was cooled slowly to room temperature over 2 hours, during which the product crystallized (if the reaction is cooled too quickly a sticky precipitate is formed instead) After filtration washing with water

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

Procedure: 56 g (0.4 Mole) of cyclohexanone enolacetate in 500 ml of methanol was ozonised in a dry ice-acetone bath until the solution turned blue. 60 ml of dimethyl sulphide was added, and the cooling bath was removed. The temperature rose slowly to 48°, and after it had returned to room temperature, 40 ml of trimethyl orthoformate and 1 ml of acetyl chloride were added. The mixture was then left for 48 h at room temperature. Three identical batches were combined and the solvent was removed in vacuo. The residue was dissolved in ether, washed with brine containing a small amount of NaHCO3, dried (Na2SO4), and distilled to give 193 g of product, b.p. 56°-69°/0.1 Torr. The NMR spectrum indicated the presence of ca. 20% of methyl 6-oxohexanoate. The product was mixed with 100 ml of trimethyl orthoformate, 20 ml of methanol, and 0.5 g of p-toluene sulfonic acid. The mixture was left for 48 h at room temperature, then worked up as above yielding 201 g (88%) of methyl 6,6-dimethoxyhexanoate. b.p. 61°/0.1 Torr.

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

Procedure: 56 g (0.4 Mole) of cyclohexanone enolacetate in 500 ml of methanol was ozonised in a dry ice-acetone bath until the solution turned blue. 60 ml of dimethyl sulphide was added, and the cooling bath was removed. The temperature rose slowly to 48°, and after it had returned to room temperature, 40 ml of trimethyl orthoformate and 1 ml of acetyl chloride were added. The mixture was then left for 48 h at room temperature. Three identical batches were combined and the solvant was removed in vacuo. The residue was dissolved in ether, washed with brine containing a small amount of NaHCO3, dried (Na2SO4), and distilled to give 193 g of product, b.p. 56°-69°/0.1 Torr. The NMR spectrum indicated the presence of ca. 20% of methyl 6-oxohexanoate. The product was mixed with 100 ml of trimethyl orthoformate, 20 ml of methanol, and 0.5 g of p-toluene sulfonic acid. The mixture was left for 48 h at room temperature, then worked up as above yielding 201 g (88%) of methyl 6,6-dimethoxyhexanoate. b.p. 61°/0.1 Torr.

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

Procedure: After the reaction, MeOH was recovered, following by the same treatment as above to give 9.47 g. of crude 6,6-dimethoxycaproic acid methyl ester. Then, a 10 wt.% aqueous hydrochloric acid solution was added to this crude product, followed by stirring for 6 hours at room temperature. The reaction mixture was treated by usual method to give crude products. Pure 3.20 g. of 5-carbomethoxy-1-pentanal was obtained by column chromatography. was recovered to give 9.47 g The reaction mixture was treated by usual method to give crude products