methyl 2-(2-methoxy-2-oxoethoxy)acetate

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of sodium hydride (60% dispersion in mineral oil. 0.30 g), dimethyl diglycolate (0.81 g) and 4-[2-[N-(2-benzoxazolyl)-N-methylamino]ethoxy]benzaldehyde (2.22 g) in dry benzene (50 mL)was stirred at room temperature overnight. Acetic acid (1 mL) was added, the mixture was poured onto iced water and extracted with ethyl acetate. The combined ethyl acetate layers were washed with water, dried (MgSO4) and evaporated. The resulting oil was chromatographed on silica gel using 2% methanol in dichloromethane, and the product crystallised from ethyl acetate, mp 111°-112° C. extracted with ethyl acetate The combined ethyl acetate layers were washed with water dried (MgSO4) evaporated The resulting oil was chromatographed on silica gel using 2% methanol in dichloromethane the product crystallised from ethyl acetate, mp 111°-112° C.

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of sodium hydride (60% dispersion in mineral oil. 0.30 g), dimethyl diglycolate (0.81 g) and 4-[2-[N-(2-benzoxazolyl)-N-methylamino]ethoxy]benzaldehyde (2.22 g) in dry benzene (50 mL) was stirred at room temperature overnight. Acetic acid (1 mL) was added, the mixture was poured onto iced water and extracted with ethyl acetate. The combined ethyl acetate layers were washed with water, dried (MgSO4) and evaporated. The resulting oil was chromatographed on silica gel using 2% methanol in dichloromethane, and the product crystallised from ethyl acetate, mp 111°-112° C. extracted with ethyl acetate The combined ethyl acetate layers were washed with water dried (MgSO4) evaporated The resulting oil was chromatographed on silica gel using 2% methanol in dichloromethane the product crystallised from ethyl acetate, mp 111°-112° C.

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of sodium hydride (60% dispersion in mineral oil, 0.30 g), dimethyl diglycolate (0.81 g) and 4-[2-[N-(2-benzoxazolyl)-N-methylamino]ethoxy]benzaldehyde (2.22 g) in dry benzene (50 mL) was stirred at room temperature overnight. Acetic acid (1 mL) was added, the mixture was poured onto iced water and extracted with ethyl acetate. The combined ethyl acetate layers were washed with water, dried (MgSO4) and evaporated. The resulting oil was chromatographed on silica gel using 2% methanol in dichloromethane, and the product crystallised from ethyl acetate, mp 111-112° C. extracted with ethyl acetate The combined ethyl acetate layers were washed with water dried (MgSO4) evaporated The resulting oil was chromatographed on silica gel using 2% methanol in dichloromethane the product crystallised from ethyl acetate, mp 111-112° C.

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of sodium hydride (60% dispersion in mineral oil. 0.30 g), dimethyl diglycolate (0.81 g) and 4-[2-[N-(2-benzoxazolyl)-N-methylamino]ethoxy]benzaldehyde (2.22 g) in dry benzene (50 mL)was stirred at room temperature overnight. Acetic acid (1 mL) was added, the mixture was poured onto iced water and extracted with ethyl acetate. The combined ethyl acetate layers were washed with water, dried (MgSO4) and evaporated. The resulting oil was chromatographed on silica gel using 2% methanol in dichloromethane, and the product crystallised from ethyl acetate, mp 111°-112° C. extracted with ethyl acetate The combined ethyl acetate layers were washed with water dried (MgSO4) evaporated The resulting oil was chromatographed on silica gel using 2% methanol in dichloromethane the product crystallised from ethyl acetate, mp 111°-112° C.

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of sodium hydride (60% dispersion in mineral oil. 0.30 g), dimethyl diglycolate (0.81 g) and 4-[2-[N-(2-benzoxazolyl)-N-methylamino]ethoxy]benzaldehyde (2.22 g) in dry benzene (50 mL)was stirred at room temperature overnight. Acetic acid (1 mL) was added, the mixture was poured onto iced water and extracted with ethyl acetate. The combined ethyl acetate layers were washed with water, dried (MgSO4) and evaporated. The resulting oil was chromatographed on silica gel using 2% methanol in dichloromethane, and the product crystallised from ethyl acetate, mp 111°-112° C. extracted with ethyl acetate The combined ethyl acetate layers were washed with water dried (MgSO4) evaporated The resulting oil was chromatographed on silica gel using 2% methanol in dichloromethane the product crystallised from ethyl acetate, mp 111°-112° C.

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of sodium hydride (60% dispersion in mineral oil. 0.30 g), dimethyl diglycolate (0.81 g) and 4-[2-[N-(2-benzoxazolyl)-N-methylamino]ethoxy]benzaldehyde (2.22 g) in dry benzene (50 mL) was stirred at room temperature overnight. Acetic acid (1 mL) was added, the mixture was poured onto iced water and extracted with ethyl acetate. The combined ethyl acetate layers were washed with water, dried (MgSO4) and evaporated. The resulting oil was chromatographed on silica gel using 2% methanol in dichloromethane, and the product crystallised from ethyl acetate, mp 111°-112° C. extracted with ethyl acetate The combined ethyl acetate layers were washed with water dried (MgSO4) evaporated The resulting oil was chromatographed on silica gel using 2% methanol in dichloromethane the product crystallised from ethyl acetate, mp 111°-112° C.

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of sodium hydride (60% dispersion in mineral oil. 0.30 g), dimethyl diglycolate (0.81 g) and 4-[2-[N-(2-benzoxazolyl)-N-methylamino]ethoxy]benzaldehyde (2.22 g) in dry benzene (50 mL) was stirred at room temperature overnight. Acetic acid (1 mL) was added, the mixture was poured onto iced water and extracted with ethyl acetate. The combined ethyl acetate layers were washed with water, dried (MgSO4) and evaporated. The resulting oil was chromatographed on silica gel using 2% methanol in dichloromethane, and the product crystallised from ethyl acetate, mp 111°-112° C. extracted with ethyl acetate The combined ethyl acetate layers were washed with water dried (MgSO4) evaporated The resulting oil was chromatographed on silica gel using 2% methanol in dichloromethane the product crystallised from ethyl acetate, mp 111°-112° C.

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 1,5 -Diamino-1,5-dibenzyloxymethyl-3 -aza-pentane (0.250 g, 0.73 mmol) (Example 6 (d)) and diglycolic acid dimethyl ester (0.118 g, 0.73 mmol) were dissolved in methanol (20 ml). The mixture was refluxed for 6 days. The solvent was evaporated and the mixture chromatographed on a silica column. 5,9-Bis(benzyloxymethyl)-1-oxa-4,7,10-triazacyclododecane-3,11-dione was isolated as a yellow oil. Yield 0.273 g (85%). FAB MS: 442 (M+1). The mixture was refluxed for 6 days The solvent was evaporated the mixture chromatographed on a silica column

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Diglycolic acid (67.05 g, 0.5 mol) was dissolved in a mixture of methanol (122 ml, 30 mol) and 1,2-dichloroethane (150 ml). KSF-catalyst (Aldrich) (2.5 g) was added and the mixture was refluxed for 15 hours. The mixture was cooled to ambient temperature, filtered through alumina, washed with aqueous saturated sodium hydrogen carbonate (100 ml) and dried over magnesium sulphate. The solvent was evaporated and diglycolic acid dimethyl ester was isolated after distillation as a colourless oil. Yield 39.5 g (49%) b.p. 65°-66° C. (0.055 mmHg). KSF-catalyst (Aldrich) (2.5 g) was added the mixture was refluxed for 15 hours filtered through alumina washed with aqueous saturated sodium hydrogen carbonate (100 ml) dried over magnesium sulphate The solvent was evaporated

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 1,5 -Diamino-1,5-dibenzyloxymethyl-3 -aza-pentane (0.250 g, 0.73 mmol) (Example 6 (d)) and diglycolic acid dimethyl ester (0.118 g, 0.73 mmol) were dissolved in methanol (20 ml). The mixture was refluxed for 6 days. The solvent was evaporated and the mixture chromatographed on a silica column. 5,9-Bis(benzyloxymethyl)-1-oxa-4,7,10-triazacyclododecane-3,11-dione was isolated as a yellow oil. Yield 0.273 g (85%). FAB MS: 442 (M+1). The mixture was refluxed for 6 days The solvent was evaporated the mixture chromatographed on a silica column

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Diglycolic acid (67.05 g, 0.5 mol) was dissolved in a mixture of methanol (122 ml, 30 mol) and 1,2-dichloroethane (150 ml). KSF-catalyst (Aldrich) (2.5 g) was added and the mixture was refluxed for 15 hours. The mixture was cooled to ambient temperature, filtered through alumina, washed with aqueous saturated sodium hydrogen carbonate (100 ml) and dried over magnesium sulphate. The solvent was evaporated and diglycolic acid dimethyl ester was isolated after distillation as a colourless oil. Yield 39.5 g (49%) b.p. 65°-66° C. (0.055 mmHg). KSF-catalyst (Aldrich) (2.5 g) was added the mixture was refluxed for 15 hours filtered through alumina washed with aqueous saturated sodium hydrogen carbonate (100 ml) dried over magnesium sulphate The solvent was evaporated

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 1,5-Diamino-1,5-dibenzyloxymethyl-3-aza-pentane (0.250 g, 0.73 mmol) (Example 6 (d)) and diglycolic acid dimethyl ester (0.118 g, 0.73 mmol) were dissolved in methanol (20 ml). The mixture was refluxed for 6 days. The solvent was evaporated and the mixture chromatographed on a silica column. 5,9-Bis(benzyloxymethyl)-1-oxa-4,7,10-triazacyclododecane-3,11-dione was isolated as a yellow oil. Yield 0.273 g (85%). FAB MS: 442(M+1). The mixture was refluxed for 6 days The solvent was evaporated the mixture chromatographed on a silica column