methyl 3,3-dimethoxypropanoate

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: (Related to methods described in Alabaster, C. T. et. al., J. Med. Chem. 1988, 31, 2048-2056.) 3,3-Dimethoxypropanoic acid methyl ester (14.25 g, 96.2 mmol) in THF (100 mL) was treated with LiOH H2O (2.5 g, 106 mmol) and H2O (2 mL). The mixture was brought to reflux for 4 hours, cooled to room temperature and azeotropically dried from THF (4 times) to provide white solids (13.3 g). to reflux for 4 hours azeotropically dried from THF (4 times)

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

Procedure: The title compound, white solid (85 mg, 77%), MS (ISP) m/z=445.3 [(M+H)+], mp 240° C., was prepared in accordance with the general method of example 81 from trans-4-{2-[4-(2,3-dihydro-benzofuran-4-yl)-piperidin-1-yl]-ethyl}-cyclohexylamine dihydrochloride (intermediate B) (100 mg, 0.25 mmol) and methyl 3,3-dimethoxy-propanoate.

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

Procedure: 50 g (0.33 mol.) of Methyl 3,3-dimethoxy-propanoate in 200 ml of 2N NaOH solution in water were refluxed 2 hours. After cooling the solution was acidified with hydrochloric acid then extracted two times with 200 ml of CH2Cl2. The extracts were dried on sodium sulfate and evaporated to leave 35 g (Yield=78%) of 3,3-dimethoxy-propanoic acid as an oil. After cooling the solution then extracted two times with 200 ml of CH2Cl2 The extracts were dried on sodium sulfate evaporated

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

Procedure: 50 g (0.33 mol.) of Methyl 3,3-dimethoxy-propanoate in 200 ml of 2N NaOH solution in water were refluxed 2 hours. After cooling the solution was acidified with hydrochloric acid then extracted two times with 200 ml of CH2Cl2. The extracts were dried on sodium sulfate and evaporated to leave 35 g (Yield=78%) of 3,3-dimethoxy-propanoic acid as an oil. After cooling the solution then extracted two times with 200 ml of CH2Cl2 The extracts were dried on sodium sulfate evaporated

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a 1.0 L RBF containing methyl 3,3-dimethoxypropanoate (17.6500 g, 119 mmol) was added THF (150 ml) and diethyl ether (150 ml), and the mixture was allowed to stir at 0° C. for 15 min. At this time, tetra-isopropoxy titanium (6.98 ml, 23.8 mmol) was added in one portion before the dropwise addition of ethylmagnesium bromide (99.3 ml, 298 mmol) via syringe. The reaction was allowed to warm to 23° C. and stir for 14 hours before being re-chilled to 0° C. After 5 min at this temp, water (15 ml) was added and a solid formed. Diethyl ether (200 ml) was added and the quenched reaction was stirred for 10 min before filtering through a plug of magnesium sulfate. The filtrate was dried with additional magnesium sulfate, filtered and concentrated to give a colorless oil. The crude material was used directly in the next reaction. to warm to 23° C. stir for 14 hours before being re-chilled to 0° C a solid formed the quenched reaction was stirred for 10 min before filtering through a plug of magnesium sulfate The filtrate was dried with additional magnesium sulfate filtered concentrated to give a colorless oil

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a 1.0 L RBF containing methyl 3,3-dimethoxypropanoate (17.6500 g, 119 mmol) was added THF (150 ml) and diethyl ether (150 ml), and the mixture was allowed to stir at 0° C. for 15 min. At this time, tetra-isopropoxy titanium (6.98 ml, 23.8 mmol) was added in one portion before the dropwise addition of ethylmagnesium bromide (99.3 ml, 298 mmol) via syringe. The reaction was allowed to warm to 23° C. and stir for 14 hours before being re-chilled to 0° C. After 5 min at this temp, water (15 ml) was added and a solid formed. Diethyl ether (200 ml) was added and the quenched reaction was stirred for 10 min before filtering through a plug of magnesium sulfate. The filtrate was dried with additional magnesium sulfate, filtered and concentrated to give a colorless oil. The crude material was used directly in the next reaction. to warm to 23° C. stir for 14 hours before being re-chilled to 0° C a solid formed the quenched reaction was stirred for 10 min before filtering through a plug of magnesium sulfate The filtrate was dried with additional magnesium sulfate filtered concentrated to give a colorless oil

Conditions: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: In a 2 liter round bottom flask equipped with a stir bar, methyl 3,3-dimethoxypropanoate (24 g, 162 mmol) was dissolved in THF (1 L). Under nitrogen, the solution was chilled to −78° C. Allyl Magnesium bromide, 1.0 M solution in diethyl ether (405 mL, 405 mmol) was added dropwise in such a way that the internal temperature remained lower than −75° C. After addition, the reaction was allowed to stir for 3 hours at −78° C. before being quenched with saturated ammonium chloride solution (300 mL). The ice bath was removed and the reaction allowed to come to RT. Water was added (200 mL) and the reaction was concentrated on a rotary evaporator to remove as much THF as possible. The product was extracted from the resulting aqueous with diethyl ether (3×200 mL). The organics were then washed with brine (100 mL), dried over magnesium sulfate, filtered and concentrated to afford the product. In a 2 liter round bottom flask equipped with a stir bar remained lower than −75° C After addition before being quenched with saturated ammonium chloride solution (300 mL) The ice bath was removed to come to RT Water was added (200 mL) the reaction was concentrated on a rotary evaporator to remove as much THF as possible The product was extracted from the resulting aqueous with diethyl ether (3×200 mL) The organics were then washed with brine (100 mL) dried over magnesium sulfate filtered concentrated to afford the product

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

Procedure: 1.7 g of 1,3,5-trimethoxybenzene, 1.68 g of methyl 3,3-dimethoxypropionate and 12 mL of glacial acetic acid were mixed, 313 mg of 35 wt % hydrochloric acid was added into the mixture at an inner temperature of 25° C., the added mixture was stirred for 1 hour at the same temperature to cause a reaction. After completion of the reaction, 36 mL of water was added dropwise into the reaction liquid, and the precipitated crystals were filtrated. The crystals were washed with 20 vol % of aqueous methanol, then, dried to obtain 2.46 g of methyl trans-3-(2,4,6-trimethoxyphenyl)acrylate (white solid). Yield: 98%. a reaction was added dropwise into the reaction liquid the precipitated crystals were filtrated The crystals were washed with 20 vol % of aqueous methanol dried

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

Procedure: 1.7 g of 1,3,5-trimethoxybenzene, 1.68 g of methyl 3,3-dimethoxypropionate and 12 mL of glacial acetic acid were mixed, 313 mg of 35 wt % hydrochloric acid was added into the mixture at an inner temperature of 25° C., the added mixture was stirred for 1 hour at the same temperature to cause a reaction. After completion of the reaction, 36 mL of water was added dropwise into the reaction liquid, and the precipitated crystals were filtrated. The crystals were washed with 20 vol % of aqueous methanol, then, dried to obtain 2.46 g of methyl trans-3-(2,4,6-trimethoxyphenyl)acrylate (white solid). Yield: 98%. a reaction was added dropwise into the reaction liquid the precipitated crystals were filtrated The crystals were washed with 20 vol % of aqueous methanol dried

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

Procedure: 1.01 g of 3-(4-fluorophenyl)-1-isopropyl-1H-indole, 0.92 g of methyl 3,3-dimethoxypropionate, 0.72 mL of 90 wt % aqueous acetic acid (containing 4 mmol of water) and 6 mL of glacial acetic acid were mixed, then, 0.33 g of phosphorus oxychloride was added dropwise into the mixture at an inner temperature of 25° C., the added mixture was stirred for 9 hours at the same temperature to cause a reaction. After completion of the reaction, 16 mL of water was added dropwise into the reaction liquid, and the precipitated crystals were filtrated. The crystals were washed with 20 vol % aqueous methanol, then, dried to obtain 1.25 g of methyl trans-3-[3-(4-fluorophenyl)-1-isopropyl-1H-indol-2-yl]acrylate (yellow solid). Yield: 93%. a reaction was added dropwise into the reaction liquid the precipitated crystals were filtrated The crystals were washed with 20 vol % aqueous methanol dried