benzyl (2S)-3-(4-hydroxyphenyl)-2-[(2-methylpropan-2-yl)oxycarbonylamino]propanoate

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

Procedure: The title compound was prepared by reaction of BocTyrOBzl (371 mg, 1 mmol) and diethylphosphorochloridate (258 mg, 1.5 mmol) with an excess of NaH (60% in mineral oil) in dry dioxane for 3.5 h at 50° C. under argon atmosphere The solvent was concentrated in vacuo and the residue was dissolved in EtOAc and washed several times with a 5% solution of NaHCO3, a 10% solution of citric acid and a solution of satured NaCl. The organic phase was dried (Na2SO4) and concentrated, giving an oil 254 mg (50% yield), that was used without purification for the next step. FAB mass spectroscopy: m/z 508 [MH]+, 530 [MNa]+. H1NMR (200 Mhz, CDCl3) d (ppm)=7.4-6.85 (m, 9H, aromatics), 5.1 (d, 2H, COOCH2—F), 4.6 (m, 1H, N—CH—CO), 4.3-4 (m, 4H, P—O—CH2—CH3), 3 (t, 2H, CH—CH2—F), 1.4 (m, 15H, CH3− CH2+ tBu). was concentrated in vacuo the residue was dissolved in EtOAc washed several times with a 5% solution of NaHCO3 The organic phase was dried (Na2SO4) concentrated

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

Procedure: The title compound was prepared by reaction of BocTyrOBzl (371 mg, 1 mmol) and diethylphosphorochloridate (258 mg, 1.5 mmol) with an excess of NaH (60% in mineral oil) in dry dioxane for 3.5 h at 50° C. under argon atmosphere The solvent was concentrated in vacuo and the residue was dissolved in EtOAc and washed several times with a 5% solution of NaHCO3, a 10% solution of citric acid and a solution of satured NaCl. The organic phase was dried (Na2SO4) and concentrated, giving an oil 254 mg (50% yield), that was used without purification for the next step. FAB mass spectroscopy: m/z 508 [MH]+, 530 [MNa]+. H1NMR (200 Mhz, CDCl3) d (ppm)=7.4-6.85 (m, 9H, aromatics), 5.1 (d, 2H, COOCH2—F), 4.6 (m, 1H, N—CH—CO), 4.3-4 (m, 4H, P—O—CH2—CH3), 3 (t, 2H, CH—CH2—F), 1.4 (m, 15H, CH3− CH2+ tBu). was concentrated in vacuo the residue was dissolved in EtOAc washed several times with a 5% solution of NaHCO3 The organic phase was dried (Na2SO4) concentrated

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

Procedure: N-Boc-L-tyrosine benzyl ester (0.371 g, 1 mmol) was dissolved in acetone (5 mL) and cesium carbonate (0.650 g, 2 mmol) was added followed by chloroacetonitrile (0.150 g, 2 mmol). The mixture was then reflux for 2 h. The reaction was cooled to room temperature and insoluble salts removed by filtration using acetone for washings. Volatiles were removed under reduced pressure and the residue dissolved in DCM. The solution was washed with brine, dried (MgSO4) and concentrated to give the desired product as an oil (450 mg). The mixture was then reflux for 2 h insoluble salts removed by filtration Volatiles were removed under reduced pressure the residue dissolved in DCM The solution was washed with brine dried (MgSO4) concentrated

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

Procedure: N-Boc-L-tyrosine benzyl ester (0.371 g, 1 mmol) was dissolved in acetone (5 mL) and cesium carbonate (0.650 g, 2 mmol) was added followed by chloroacetonitrile (0.150 g, 2 mmol). The mixture was then reflux for 2 h. The reaction was cooled to room temperature and insoluble salts removed by filtration using acetone for washings. Volatiles were removed under reduced pressure and the residue dissolved in DCM. The solution was washed with brine, dried (MgSO4) and concentrated to give the desired product as an oil (450 mg). The mixture was then reflux for 2 h insoluble salts removed by filtration Volatiles were removed under reduced pressure the residue dissolved in DCM The solution was washed with brine dried (MgSO4) concentrated

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

Procedure: N-Boc-L-tyrosine benzyl ester (0.371 g, 1 mmol) was dissolved in acetone (5 mL) and cesium carbonate (0.650 g, 2 mmol) was added followed by chloroacetonitrile (0.150 g, 2 mmol). The mixture was then reflux for 2 h. The reaction was cooled to room temperature and insoluble salts removed by filtration using acetone for washings. Volatiles were removed under reduced pressure and the residue dissolved in DCM. The solution was washed with brine, dried (MgSO4) and concentrated to give the desired product as an oil (450 mg). The mixture was then reflux for 2 h insoluble salts removed by filtration Volatiles were removed under reduced pressure the residue dissolved in DCM The solution was washed with brine dried (MgSO4) concentrated

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

Procedure: N-Boc-L-tyrosine benzyl ester (0.371 g, 1 mmol) was dissolved in acetone (5 mL) and cesium carbonate (0.650 g, 2 mmol) was added followed by chloroacetonitrile (0.150 g, 2 mmol). The mixture was then reflux for 2 h. The reaction was cooled to room temperature and insoluble salts removed by filtration using acetone for washings. Volatiles were removed under reduced pressure and the residue dissolved in DCM. The solution was washed with brine, dried (MgSO4) and concentrated to give the desired product as an oil (450 mg). The mixture was then reflux for 2 h insoluble salts removed by filtration Volatiles were removed under reduced pressure the residue dissolved in DCM The solution was washed with brine dried (MgSO4) concentrated

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

Procedure: N-Boc-L-tyrosine benzyl ester (0.371 g, 1 mmol) was dissolved in acetone (5 mL) and cesium carbonate (0.650 g, 2 mmol) was added followed by chloroacetonitrile (0.150 g, 2 mmol). The mixture was then reflux for 2 h. The reaction was cooled to room temperature and insoluble salts removed by filtration using acetone for washings. Volatiles were removed under reduced pressure and the residue dissolved in DCM. The solution was washed with brine, dried (MgSO4) and concentrated to give the desired product as an oil (450 mg). The mixture was then reflux for 2 h insoluble salts removed by filtration Volatiles were removed under reduced pressure the residue dissolved in DCM The solution was washed with brine dried (MgSO4) concentrated

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

Procedure: The title compound was prepared by reaction of BocTyrOBzl (371 mg, 1 mmol) and diethylphosphorochloridate (258 mg, 1.5 mmol) with an excess of NaH (60% in mineral oil) in dry dioxane for 3.5 h at 50° C. under argon atmosphere The solvent was concentrated in vacuo and the residue was dissolved in EtOAc and washed several times with a 5% solution of NaHCO3, a 10% solution of citric acid and a solution of satured NaCl. The organic phase was dried (Na2SO4) and concentrated, giving an oil 254 mg (50% yield), that was used without purification for the next step. FAB mass spectroscopy: m/z 508 [MH]+, 530 [MNa]+. H1NMR (200 Mhz, CDCl3) d (ppm)=7.4-6.85 (m, 9H, aromatics), 5.1 (d, 2H, COOCH2—F), 4.6 (m, 1H, N—CH—CO), 4.3-4 (m, 4H, P—O—CH2—CH3), 3 (t, 2H, CH—CH2—F), 1.4 (m, 15H, CH3− CH2+ tBu). was concentrated in vacuo the residue was dissolved in EtOAc washed several times with a 5% solution of NaHCO3 The organic phase was dried (Na2SO4) concentrated

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

Procedure: N-Boc-L-tyrosine benzyl ester (0.371 g, 1 mmol) was dissolved in acetone (5 mL) and cesium carbonate (0.650 g, 2 mmol) was added followed by chloroacetonitrile (0.150 g, 2 mmol). The mixture was then reflux for 2 h. The reaction was cooled to room temperature and insoluble salts removed by filtration using acetone for washings. Volatiles were removed under reduced pressure and the residue dissolved in DCM. The solution was washed with brine, dried (MgSO4) and concentrated to give the desired product as an oil (450 mg). The mixture was then reflux for 2 h insoluble salts removed by filtration Volatiles were removed under reduced pressure the residue dissolved in DCM The solution was washed with brine dried (MgSO4) concentrated

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

Procedure: N-Boc-L-tyrosine benzyl ester (0.371 g, 1 mmol) was dissolved in acetone (5 mL) and cesium carbonate (0.650 g, 2 mmol) was added followed by chloroacetonitrile (0.150 g, 2 mmol). The mixture was then reflux for 2 h. The reaction was cooled to room temperature and insoluble salts removed by filtration using acetone for washings. Volatiles were removed under reduced pressure and the residue dissolved in DCM. The solution was washed with brine, dried (MgSO4) and concentrated to give the desired product as an oil (450 mg). The mixture was then reflux for 2 h insoluble salts removed by filtration Volatiles were removed under reduced pressure the residue dissolved in DCM The solution was washed with brine dried (MgSO4) concentrated