(S)-1-tert-Butyl 5-methyl 2-((tert-butoxycarbonyl)amino)pentanedioate

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

Procedure: 13.4 g of Boc-Glu(OMe)-OtBu (˜39.6 mmol) are dissolved in 30 mL of acetonitrile and treated with 986 mg of DMAP (7.91 mmol, 0.2 eq). Under nitrogen atmosphere a solution of 17.6 g of di-tert-butylbicarbonate (77.1 mmol, 2 eq) in 100 mL of acetonitrile is added. After stirring overnight, the solvent is removed in vacuo and the obtained crude product is purified by chromatography on silica gel (column: 31*6.0 cm, petroleum ether/ethyl acetate 9:1) the solvent is removed in vacuo the obtained crude product is purified by chromatography on silica gel (column: 31*6.0 cm, petroleum ether/ethyl acetate 9:1)

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

Procedure: 12.0 g of Boc-Glu-OtBu (39.6 mmol) are dissolved in 200 mL of DMF. Under argon atmosphere, 7.09 g of cesium carbonate (21.8 mmol, 0.55 eq.) are added and the resulting suspension is stirred for 1 hour at RT. After this time, 2.47 mL of methyl iodide (39.6 mmol) are added and stirred at RT overnight. The solvent is removed in vacuo and the obtained residue is taken up in 400 mL of ethyl acetate. The undissolved solid is filtered and the filtrate is washed with respectively 75 mL of 10% citric acid, 10% NaHCO3 solution and brine 3 times. After drying of the organic phase over Na2SO4 the solvent is removed in vacuo. The product is obtained as yellow oil. The product can be used without further purification in the following reaction. stirred at RT overnight The solvent is removed in vacuo The undissolved solid is filtered the filtrate is washed with respectively 75 mL of 10% citric acid, 10% NaHCO3 solution and brine 3 times After drying of the organic phase over Na2SO4 the solvent is removed in vacuo The product is obtained as yellow oil The product can be used without further purification in the following reaction

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

Procedure: 13.4 g of Boc-Glu(OMe)-OtBu (˜39.6 mmol) are dissolved in 30 mL of acetonitrile and treated with 986 mg of DMAP (7.91 mmol, 0.2 eq). Under nitrogen atmosphere a solution of 17.6 g of di-tert-butylbicarbonate (77.1 mmol, 2 eq) in 100 mL of acetonitrile is added. After stirring overnight, the solvent is removed in vacuo and the obtained crude product is purified by chromatography on silica gel (column: 31*6.0 cm, petroleum ether/ethyl acetate 9:1) the solvent is removed in vacuo the obtained crude product is purified by chromatography on silica gel (column: 31*6.0 cm, petroleum ether/ethyl acetate 9:1)

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

Procedure: 12.0 g of Boc-Glu-OtBu (39.6 mmol) are dissolved in 200 mL of DMF. Under argon atmosphere, 7.09 g of cesium carbonate (21.8 mmol, 0.55 eq.) are added and the resulting suspension is stirred for 1 hour at RT. After this time, 2.47 mL of methyl iodide (39.6 mmol) are added and stirred at RT overnight. The solvent is removed in vacuo and the obtained residue is taken up in 400 mL of ethyl acetate. The undissolved solid is filtered and the filtrate is washed with respectively 75 mL of 10% citric acid, 10% NaHCO3 solution and brine 3 times. After drying of the organic phase over Na2SO4 the solvent is removed in vacuo. The product is obtained as yellow oil. The product can be used without further purification in the following reaction. stirred at RT overnight The solvent is removed in vacuo The undissolved solid is filtered the filtrate is washed with respectively 75 mL of 10% citric acid, 10% NaHCO3 solution and brine 3 times After drying of the organic phase over Na2SO4 the solvent is removed in vacuo The product is obtained as yellow oil The product can be used without further purification in the following reaction

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

Procedure: 13.4 g of Boc-Glu(OMe)-OtBu (˜39.6 mmol) are dissolved in 30 mL of acetonitrile and treated with 986 mg of DMAP (7.91 mmol, 0.2 eq). Under nitrogen atmosphere a solution of 17.6 g of di-tert-butylbicarbonate (77.1 mmol, 2 eq) in 100 mL of acetonitrile is added. After stirring overnight, the solvent is removed in vacuo and the obtained crude product is purified by chromatography on silica gel (column: 31*6.0 cm, petroleum ether/ethyl acetate 9:1) the solvent is removed in vacuo the obtained crude product is purified by chromatography on silica gel (column: 31*6.0 cm, petroleum ether/ethyl acetate 9:1)

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

Procedure: 12.0 g of Boc-Glu-OtBu (39.6 mmol) are dissolved in 200 mL of DMF. Under argon atmosphere, 7.09 g of cesium carbonate (21.8 mmol, 0.55 eq.) are added and the resulting suspension is stirred for 1 hour at RT. After this time, 2.47 mL of methyl iodide (39.6 mmol) are added and stirred at RT overnight. The solvent is removed in vacuo and the obtained residue is taken up in 400 mL of ethyl acetate. The undissolved solid is filtered and the filtrate is washed with respectively 75 mL of 10% citric acid, 10% NaHCO3 solution and brine 3 times. After drying of the organic phase over Na2SO4 the solvent is removed in vacuo. The product is obtained as yellow oil. The product can be used without further purification in the following reaction. stirred at RT overnight The solvent is removed in vacuo The undissolved solid is filtered the filtrate is washed with respectively 75 mL of 10% citric acid, 10% NaHCO3 solution and brine 3 times After drying of the organic phase over Na2SO4 the solvent is removed in vacuo The product is obtained as yellow oil The product can be used without further purification in the following reaction

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

Procedure: 1.3 g of N-tert.-butyloxycarbonyl-L-glutamic acid 5-methyl ester 1-tert.-butyl ester (1.2., 4.12 mmol) are dissolved in 15 ml of acetonitrile and mixed with 100 mg of N,N-dimethyl-4-aminopyridine (DMAP). A solution of 1.79 g of di-tert.-butyl-bicarbonate (8.2 mmol) in 7 ml of acetonitrile is added under nitrogen atmosphere. After stirring overnight, the solvent is removed under vacuum and the crude product obtained is purified by means of chromatography on silica gel. the solvent is removed under vacuum

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

Procedure: 2.3 g of N-tert.butyloxycarbonyl-L-glutamic acid 1-tert.-butyl ester (7.58 mmol) are dissolved in 80 ml of methanol and a freshly prepared diazomethane solution (23 mmol of Diazald®) is added dropwise at room temperature. After one hour, the solvent is removed under vacuum. The compound is purified using chromatography on silica gel. (column: 18.5*4 cm, DCM/MeOH=99/1, Rf=0.99). the solvent is removed under vacuum The compound is purified