甲氧基乙酸异丙酯

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A dry solution of 2.1 g (11.2 mmole) trans-1-amino-2-(2,2-dimethoxyethyl)-cyclohexane and 1.38 g (10.4 mmole) methoxy acetic acid isopropyl ester in 20 ml MTBE was mixed with 200 mg immobilized lipase Novozym® 435 and shaken for 25 hours at room temperature. After this period of time the conversion was 49.5%. The (1R, 2S)-enantiomer was acylated to the methoxy acetamide, while the (1S, 2R)-enantiomer was not acylated. After removal of the enzyme by filtration, removal of the solvent using an rotary evaporator and purification by column chromatography (silica gel, eluation starting with MTSE and finally with MTBE/methanol)970 mg of pure (1S, 2R)-1-amino-2-(2,2-dimethoxyethyl)-cyclohexane (46% yield) were obtained. After this period of time the conversion was After removal of the enzyme by filtration, removal of the solvent an rotary evaporator and purification by column chromatography (silica gel, eluation

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: 50 g (0.32 mol) of methyl trans-2-aminocyclohexanecarboxylate were dissolved in 200 ml of MTBE and, after addition of 0.16 mol of isopropyl methoxyacetate and 0.5 g of Novozym 435 (Novo Nordisk), shaken at room temperature for 8 h. The enzyme was filtered off and then the solvent was removed and the residue was distilled under reduced pressure. 23.5 g of methyl (1S,2S)-2-aminocyclohexanecarboxylate and 35.2 g of methyl (1R,2R)-2-(2-methoxyacetylamino) cyclohexanecarboxylate were obtained, each with an ee of 99.8%. The ee of the amine was determined after N-acylation with acetic anhydride by gas chromatography on a B-PH GC column (supplied by Astec, N.J., USA), while the N-2-methoxyacetamide was put on this column without derivatization. The enzyme was filtered off the solvent was removed the residue was distilled under reduced pressure

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A dry solution of 2.1 g (11.2 mmole) trans-1-amino-2-(2,2-dimethoxyethyl)-cyclohexane and 1.38 g (10.4 mmole) methoxy acetic acid isopropyl ester in 20 ml MTBE was mixed with 200 mg immobilized lipase Novozym® 435 and shaken for 25 hours at room temperature. After this period of time the conversion was 49.5%. The (1R, 2S)-enantiomer was acylated to the methoxy acetamide, while the (1S, 2R)-enantiomer was not acylated. After removal of the enzyme by filtration, removal of the solvent using an rotary evaporator and purification by column chromatography (silica gel, eluation starting with MTSE and finally with MTBE/methanol)970 mg of pure (1S, 2R)-1-amino-2-(2,2-dimethoxyethyl)-cyclohexane (46% yield) were obtained. After this period of time the conversion was After removal of the enzyme by filtration, removal of the solvent an rotary evaporator and purification by column chromatography (silica gel, eluation

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A dry solution of 2.1 g (11.2 mmole) trans-1-amino-2-(2,2-dimethoxyethyl)-cyclohexane and 1.38 g (10.4 mmole) methoxy acetic acid isopropyl ester in 20 ml MTBE was mixed with 200 mg immobilized lipase Novozym® 435 and shaken for 25 hours at room temperature. After this period of time the conversion was 49.5%. The (1R, 2S)-enantiomer was acylated to the methoxy acetamide, while the (1S, 2R)-enantiomer was not acylated. After removal of the enzyme by filtration, removal of the solvent using an rotary evaporator and purification by column chromatography (silica gel, eluation starting with MTSE and finally with MTBE/methanol)970 mg of pure (1S, 2R)-1-amino-2-(2,2-dimethoxyethyl)-cyclohexane (46% yield) were obtained. After this period of time the conversion was After removal of the enzyme by filtration, removal of the solvent an rotary evaporator and purification by column chromatography (silica gel, eluation

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: 1-(3-tert-Butoxyphenyl)ethylamine (86 g, 0.45 mol) was admixed with isopropyl methoxyacetate (129 g, 0.98 mol) and Novozyme® 435 (0.9 g), and stirred at room temperature for 16 h. The subsequent analysis of the optical purity showed that the S enantiomer of 1-(3-tert-butoxyphenyl)ethylamine was enantiomerically pure. The acylated R enantiomer had an optical purity of 99.1%. The mixture was filtered through kieselguhr and washed with toluene (200 ml), and the filtrate was concentrated at 40° C. on a rotary evaporator. The residue was taken up in toluene (200 ml) and admixed dropwise with 37% sulfuric acid (29.5 g, 0.12 mol). A greasy, unfilterable precipitate formed, which was dissolved in water (250 ml). The aqueous solution was washed 3 times with 50 ml each time of toluene. The combined organic phases were washed once with 50 ml of water and then dried over sodium sulfate. After the solvent had been removed, the residue was freed of further volatile constituents in an oil-pump vacuum at 0.5 bar and 85° C. 70 g of crude (R)—N-1-(3-tert-butoxyphenyl)ethylmethoxyacetamide were obtained, whose chemical purity, according to GC analysis, was 93%. The optical purity was 99% ee. The mixture was filtered through kieselguhr washed with toluene (200 ml) the filtrate was concentrated at 40° C. on a rotary evaporator A greasy, unfilterable precipitate formed The aqueous solution was washed 3 times with 50 ml each time of toluene The combined organic phases were washed once with 50 ml of water dried over sodium sulfate After the solvent had been removed was freed of further volatile constituents in an oil-pump vacuum at 0.5 bar and 85° C

反应条件: temp:25.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: 434.1 g (4.0 mol) of methyl chloroacetate are initially introduced and stirred at 25° C. 756.3 g (4.2 mol) of 30% strength sodium methoxide solution are added dropwise in the course of 2.5 h such that a reaction temperature of 65° C. is not exceeded. After the addition, stirring is continued at reflux temperature for a further 3 h. 407.5 g of methanol are then separated from the reaction mixture by distillation. 480.8 g (8 mol) of isopropanol are added to the residue and the mixture is heated under reflux. In the course of this, methanol is removed through a 0.5 m long Multifil column at a reflux ratio of approximately 1:1 (291.9 g of distillate). After 6.5 h, the conversion of the methyl methoxyacetate to the isopropyl methoxyacetate is >98%. After cooling, the reaction mixture is filtered off with suction and the residue is washed with 450 g of isopropanol. A residue of 412.1 g and a liquid phase (filtrate and wash liquid) of 969.9 g are obtained. The liquid phase is fractionated through a 0.5 m long Multifil column. Isopropyl methoxyacetate (405.0 g, yield 77%) with an organic purity of >99%, a chlorine content of 10 ppm and a water content of <0.05% is obtained as the main fraction. After the addition stirring at reflux temperature for a further 3 h 407.5 g of methanol are then separated from the reaction mixture by distillation the mixture is heated under reflux In the course of this, methanol is removed through a 0.5 m long Multifil column at a reflux ratio of approximately 1:1 (291.9 g of distillate) After cooling the reaction mixture is filtered off with suction the residue is washed with 450 g of isopropanol A residue of 412.1 g and a liquid phase (filtrate and wash liquid) of 969.9 g are obtained

反应条件: temp:25.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: 434.1 g (4.0 mol) of methyl chloroacetate are initially introduced and stirred at 25° C. 756.3 g (4.2 mol) of 30% strength sodium methoxide solution are added dropwise in the course of 2.5 h such that a reaction temperature of 65° C. is not exceeded. After the addition, stirring is continued at reflux temperature for a further 3 h. 436.0 g of methanol are then removed from the reaction mixture by distillation. 480.8 g (8 mol) of isopropanol are added to the residue and the mixture is heated under reflux. In the course of this, methanol is removed via a 0.5 m long Multifil column at a reflux ratio of approximately 1:1 (244.4 g of distillate). After 6.5 h, the conversion of the methyl methoxyacetate to the isopropyl methoxyacetate is >98%. After cooling, the reaction mixture is concentrated to dryness on a rotary evaporator at a maximum bath temperature of 120° C. and a pressure of <15 mbar. A residue of 274.3 g and a distillate of 668.0 g are obtained. The distillate is fractionated through a 0.5 m long Multifil column. Isopropyl methoxyacetate is obtained as the main fraction (390.6 g, yield 74%) with a purity of >99%, a chlorine content of 10 ppm and a water content of <0.05%. After the addition stirring at reflux temperature for a further 3 h 436.0 g of methanol are then removed from the reaction mixture by distillation the mixture is heated under reflux In the course of this, methanol is removed via a 0.5 m long Multifil column at a reflux ratio of approximately 1:1 (244.4 g of distillate) After cooling the reaction mixture is concentrated to dryness on a rotary evaporator at a maximum bath temperature of 120° C. A residue of 274.3 g and a distillate of 668.0 g are obtained

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: 50 g (0.32 mol) of methyl trans-2-aminocyclohexanecarboxylate were dissolved in 200 ml of MTBE and, after addition of 0.16 mol of isopropyl methoxyacetate and 0.5 g of Novozym 435 (Novo Nordisk), shaken at room temperature for 8 h. The enzyme was filtered off and then the solvent was removed and the residue was distilled under reduced pressure. 23.5 g of methyl (1S,2S)-2-aminocyclohexanecarboxylate and 35.2 g of methyl (1R,2R)-2-(2-methoxyacetylamino) cyclohexanecarboxylate were obtained, each with an ee of 99.8%. The ee of the amine was determined after N-acylation with acetic anhydride by gas chromatography on a B-PH GC column (supplied by Astec, N.J., USA), while the N-2-methoxyacetamide was put on this column without derivatization. The enzyme was filtered off the solvent was removed the residue was distilled under reduced pressure

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A dry solution of 2.1 g (11.2 mmole) trans-1-amino-2-(2,2-dimethoxyethyl)-cyclohexane and 1.38 g (10.4 mmole) methoxy acetic acid isopropyl ester in 20 ml MTBE was mixed with 200 mg immobilized lipase Novozym® 435 and shaken for 25 hours at room temperature. After this period of time the conversion was 49.5%. The (1R, 2S)-enantiomer was acylated to the methoxy acetamide, while the (1S, 2R)-enantiomer was not acylated. After removal of the enzyme by filtration, removal of the solvent using an rotary evaporator and purification by column chromatography (silica gel, eluation starting with MTSE and finally with MTBE/methanol)970 mg of pure (1S, 2R)-1-amino-2-(2,2-dimethoxyethyl)-cyclohexane (46% yield) were obtained. After this period of time the conversion was After removal of the enzyme by filtration, removal of the solvent an rotary evaporator and purification by column chromatography (silica gel, eluation