1-tert-Butyl 18-(2,5-dioxopyrrolidin-1-yl) octadecanedioate

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

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

実験手順: 3-(Benzyloxycarbonylmethylamino)propionic acid tert-butyl ester (0.030 g, 0.1 mmol) and octadecanedioic acid tert-butyl ester 2,5-dioxo-pyrrolidin-1-yl ester (0.050 mg, 0.1 mmol) was suspended in dry DMF (1 ml). HOAt (0.014 g, 0.1 mmol) and DIPEA (0.21 ml, 1.2 mmol) was added. The yellow reaction mixture was stirred under nitrogen for 42 h. The reaction mixture was concentrated. The residue was redissolved in EtOAc and washed with 0.1 N HCl (2×), water (1×), dried (Na2SO4) and concentrated to give 17-[Benzyloxycarbonylmethyl-(2-tert-butoxycarbonyl-ethyl)-carbamoyl]-heptadecanoic acid tert-butyl ester in 85% yield (55 mg). The reaction mixture was concentrated The residue was redissolved in EtOAc washed with 0.1 N HCl (2×), water (1×) dried (Na2SO4) concentrated

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

実験手順: 3-(Benzyloxycarbonylmethylamino)propionic acid tert-butyl ester (0.030 g, 0.1 mmol) and octadecanedioic acid tert-butyl ester 2,5-dioxo-pyrrolidin-1-yl ester (0.050 mg, 0.1 mmol) was suspended in dry DMF (1 ml). HOAt (0.014 g, 0.1 mmol) and DIPEA (0.21 ml, 1.2 mmol) was added. The yellow reaction mixture was stirred under nitrogen for 42 h. The reaction mixture was concentrated. The residue was redissolved in EtOAc and washed with 0.1 N HCl (2×), water (1×), dried (Na2SO4) and concentrated to give 17-[Benzyloxycarbonylmethyl-(2-tert-butoxycarbonyl-ethyl)-carbamoyl]-heptadecanoic acid tert-butyl ester in 85% yield (55 mg). The reaction mixture was concentrated The residue was redissolved in EtOAc washed with 0.1 N HCl (2×), water (1×) dried (Na2SO4) concentrated

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

実験手順: 3-(Benzyloxycarbonylmethylamino)propionic acid tert-butyl ester (0,030 g, 0.1 mmol) and octadecanedioic acid tert-butyl ester 2,5-dioxo-pyrrolidin-1-yl ester (0,050 mg, 0.1 mmol) was suspended in dry DMF (1 ml). HOAt (0.014 g, 0.1 mmol) and DIPEA (0.21 ml, 1.2 mmol) was added. The yellow reaction mixture was stirred under nitrogen for 42 h. The reaction mixture was concentrated. The residue was redissolved in EtOAc and washed with 0.1 N HCl (2×), water (1×), dried (Na2SO4) and concentrated to give 17-[Benzyloxycarbonylmethyl-(2-tert-butoxycarbonyl-ethyl)-carbamoyl]-heptadecanoic acid tert-butyl ester in 85% yield (55 mg). The reaction mixture was concentrated The residue was redissolved in EtOAc washed with 0.1 N HCl (2×), water (1×) dried (Na2SO4) concentrated

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

実験手順: Octadecanedioic acid mono-tert-butyl ester (4.2 g, 0.011 mol) was dissolved in THF (20 mL), TSTU (4 g, 0.013 mol) in acetonitrile (20 mL) was added and pH of the solution was adjusted to 8 with dropwise addition of DIPEA. The mixture was stirred at RT for 4 h, then acidified with HCl (2M) to pH 3 and evaporated in vacuo. The residual oil was subsequently partitioned between ethyl acetate and HCl (0.1 M). The organic layer was dried (MgSO4), filtered and evaporated to dryness in vacuo. This afforded 5.2 g of octadecanedioic acid tert-butyl ester 2,5-dioxopyrrolidin-1-yl ester as an oil, which could be used in the next step without further purification. LC-MS (electrospray): m/z=468 (M+1) and 412 (M+1-tBu). evaporated in vacuo The residual oil was subsequently partitioned between ethyl acetate and HCl (0.1 M) The organic layer was dried (MgSO4) filtered evaporated to dryness in vacuo This afforded 5.2 g of octadecanedioic acid tert-butyl ester 2,5-dioxopyrrolidin-1-yl ester as an oil, which could be used in the next step without further purification

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

実験手順: Octadecanedioic acid mono-tert-butyl ester (4.2 g, 0.011 mol) was dissolved in THF (20 mL), TSTU (4 g, 0.013 mol) in acetonitrile (20 mL) was added and pH of the solution was adjusted to 8 with dropwise addition of DIPEA. The mixture was stirred at RT for 4 h, then acidified with HCl (2M) to pH 3 and evaporated in vacuo. The residual oil was subsequently partitioned between ethyl acetate and HCl (0.1 M). The organic layer was dried (MgSO4), filtered and evaporated to dryness in vacuo. This afforded 5.2 g of octadecanedioic acid tert-butyl ester 2,5-dioxopyrrolidin-1-yl ester as an oil, which could be used in the next step without further purification. LC-MS (electrospray): m/z=468 (M+1) and 412 (M+1-tBu). evaporated in vacuo The residual oil was subsequently partitioned between ethyl acetate and HCl (0.1 M) The organic layer was dried (MgSO4) filtered evaporated to dryness in vacuo This afforded 5.2 g of octadecanedioic acid tert-butyl ester 2,5-dioxopyrrolidin-1-yl ester as an oil, which could be used in the next step without further purification

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

実験手順: Octadecanedioic acid mono-tert-butyl ester (4.2 g, 0.011 mol) was dissolved in THF (20 mL), TSTU (4 g, 0.013 mol) in acetonitrile (20 mL) was added and pH of the solution was adjusted to 8 with dropwise addition of DIPEA. The mixture was stirred at RT for 4 h, then acidified with HCl (2M) to pH 3 and evaporated in vacuo. The residual oil was subsequently partitioned between ethyl acetate and HCl (0.1 M). The organic layer was dried (MgSO4), filtered and evaporated to dryness in vacuo. This afforded 5.2 g of octadecanedioic acid tert-butyl ester 2,5-dioxopyrrolidin-1-yl ester as an oil, which could be used in the next step without further purification. LC-MS (electrospray): m/z=468 (M+1) and 412 (M+1-tBu). evaporated in vacuo The residual oil was subsequently partitioned between ethyl acetate and HCl (0.1 M) The organic layer was dried (MgSO4) filtered evaporated to dryness in vacuo This afforded 5.2 g of octadecanedioic acid tert-butyl ester 2,5-dioxopyrrolidin-1-yl ester as an oil, which could be used in the next step without further purification

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

実験手順: To a solution of mono-tert-butyl octadecanedioate (1,00 g, 2.7 mmol) in dry THF (8 ml), was added DIPEA (0,555 ml, 3.2 mmol) followed by TSTU (1,00 g, 3.2 mmol). The reaction mixture was stirred under nitrogen for 18 h. The solvent had evaporated. AcOEt was added to the residue and the resulting suspension was filtered. The filtrate was washed with cold 0.1 M HCl (2×) and water, dried and concentrated to give succinimidyl tert-butyl octadecandioate as a white solid. The solvent had evaporated AcOEt was added to the residue the resulting suspension was filtered The filtrate was washed with cold 0.1 M HCl (2×) and water dried concentrated

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

実験手順: To a solution of mono-tert-butyl octadecanedioate (1.00 g, 2.7 mmol) in dry THF (8 ml), was added DIPEA (0,555 ml, 3.2 mmol) followed by TSTU (1.00 g, 3.2 mmol). The reaction mixture was stirred under nitrogen for 18 h. The solvent had evaporated. AcOEt was added to the residue and the resulting suspension was filtered. The filtrate was washed with cold 0.1 M HCl (2×) and water, dried and concentrated to give succinimidyl tert-butyl octadecandioate as a white solid. The solvent had evaporated AcOEt was added to the residue the resulting suspension was filtered The filtrate was washed with cold 0.1 M HCl (2×) and water dried concentrated

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

実験手順: 3-(Benzyloxycarbonylmethylamino)propionic acid tert-butyl ester (0.030 g, 0.1 mmol) and octadecanedioic acid tert-butyl ester 2,5-dioxo-pyrrolidin-1-yl ester (0.050 mg, 0.1 mmol) was suspended in dry DMF (1 ml). HOAt (0.014 g, 0.1 mmol) and DIPEA (0.21 ml, 1.2 mmol) was added. The yellow reaction mixture was stirred under nitrogen for 42 h. The reaction mixture was concentrated. The residue was redissolved in EtOAc and washed with 0.1 N HCl (2×), water (1×), dried (Na2SO4) and concentrated to give 17-[Benzyloxycarbonylmethyl-(2-tert-butoxycarbonyl-ethyl)-carbamoyl]-heptadecanoic acid tert-butyl ester in 85% yield (55 mg). The reaction mixture was concentrated The residue was redissolved in EtOAc washed with 0.1 N HCl (2×), water (1×) dried (Na2SO4) concentrated

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

実験手順: 3-(Benzyloxycarbonylmethylamino)propionic acid tert-butyl ester (0,030 g, 0.1 mmol) and octadecanedioic acid tert-butyl ester 2,5-dioxo-pyrrolidin-1-yl ester (0,050 mg, 0.1 mmol) was suspended in dry DMF (1 ml). HOAt (0.014 g, 0.1 mmol) and DIPEA (0.21 ml, 1.2 mmol) was added. The yellow reaction mixture was stirred under nitrogen for 42 h. The reaction mixture was concentrated. The residue was redissolved in EtOAc and washed with 0.1 N HCl (2×), water (1×), dried (Na2SO4) and concentrated to give 17-[Benzyloxycarbonylmethyl-(2-tert-butoxycarbonyl-ethyl)-carbamoyl]-heptadecanoic acid tert-butyl ester in 85% yield (55 mg). The reaction mixture was concentrated The residue was redissolved in EtOAc washed with 0.1 N HCl (2×), water (1×) dried (Na2SO4) concentrated