tert-butyl (2S)-3-(4-hydroxyphenyl)-2-(phenylmethoxycarbonylamino)propanoate

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a 0° C. suspension of L-tyrosine tert-butyl ester (Bachem, 1.0 eq) and sodium bicarbonate (2.0 eq) in a 1:1 mixture of THF and water was added slowly with stirring benzyl chloroformate (1.1 eq). After the addition, the mixture was stirred at 0° C. for 3 h and at room temperature for 24 h. The mixture was diluted with diethyl ether, and the aqueous layer was separated. The organic extracts were washed with saturated sodium chloride, treated with anhydrous magnesium sulfate, filtered, and evaporated to afford N-benzyloxycarbonyl-L-tyrosine tert-butyl ester of sufficient purity for immediate conversion of the tyrosine hydroxyl into a carbamate. After the addition the aqueous layer was separated The organic extracts were washed with saturated sodium chloride treated with anhydrous magnesium sulfate filtered evaporated

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a 0° C. suspension of L-tyrosine tert-butyl ester (Bachem, 1.0 eq) and sodium bicarbonate (2.0 eq) in a 1:1 mixture of THF and water was added slowly with stirring benzyl chloroformate (1.1 eq). After the addition, the mixture was stirred at 0° C. for 3 h and at room temperature for 24 h. The mixture was diluted with diethyl ether, and the aqueous layer was separated. The organic extracts were washed with saturated sodium chloride, treated with anhydrous magnesium sulfate, filtered, and evaporated to afford N-benzyloxycarbonyl-L-tyrosine tert-butyl ester of sufficient purity for immediate conversion of the tyrosine hydroxyl into a carbamate. After the addition the aqueous layer was separated The organic extracts were washed with saturated sodium chloride treated with anhydrous magnesium sulfate filtered evaporated

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a 0° C. suspension of L-tyrosine tert-butyl ester (Bachem, 1.0 eq) and sodium bicarbonate (2.0 eq) in a 1:1 mixture of THF and water was added slowly with stirring benzyl chloroformate (1.1 eq). After the addition, the mixture was stirred at 0° C. for 3 h and at room temperature for 24 h. The mixture was diluted with diethyl ether, and the aqueous layer was separated. The organic extracts were washed with saturated sodium chloride, treated with anhydrous magnesium sulfate, filtered, and evaporated to afford N-benzyloxycarbonyl-L-tyrosine tert-butyl ester of sufficient purity for immediate conversion of the tyrosine hydroxyl into a carbamate. After the addition the aqueous layer was separated The organic extracts were washed with saturated sodium chloride treated with anhydrous magnesium sulfate filtered evaporated

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a 0° C. suspension of L-tyrosine tert-butyl ester (Bachem, 1.0 eq) and sodium bicarbonate (2.0 eq) in a 1:1 mixture of THF and water was added slowly with stirring benzyl chloroformate (1.1 eq). After the addition, the mixture was stirred at 0° C. for 3 h and at room temperature for 24 h. The mixture was diluted with diethyl ether, and the aqueous layer was separated. The organic extracts were washed with saturated sodium chloride, treated with anhydrous magnesium sulfate, filtered, and evaporated to afford N-benzyloxycarbonyl-L-tyrosine tert-butyl ester of sufficient purity for immediate conversion of the tyrosine hydroxyl into a carbamate. After the addition the aqueous layer was separated The organic extracts were washed with saturated sodium chloride treated with anhydrous magnesium sulfate filtered evaporated

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a 0° C. suspension of L-tyrosine tert-butyl ester (Bachem, 1.0 eq) and sodium bicarbonate (2.0 eq) in a 1:1 mixture of THF and water was added slowly with stirring benzyl chloroformate (1.1 eq). After the addition, the mixture was stirred at 0° C. for 3 h and at room temperature for 24 h. The mixture was diluted with diethyl ether, and the aqueous layer was separated. The organic extracts were washed with saturated sodium chloride, treated with anhydrous magnesium sulfate, filtered, and evaporated to afford N-benzyloxycarbonyl-L-tyrosine tert-butyl ester of sufficient purity for immediate conversion of the tyrosine hydroxyl into a carbamate. After the addition the aqueous layer was separated The organic extracts were washed with saturated sodium chloride treated with anhydrous magnesium sulfate filtered evaporated

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a 0° C. suspension of L-tyrosine tert-butyl ester (Bachem, 1.0. eq) and sodium bicarbonate (2.0 eq) in a 1:1 mixture of THF and water was added slowly with stirring benzyl chloroformate (1. 1 eq). After the addition, the mixture was stirred at 0° C. for 3 h and at room temperature for 24 h. The mixture was diluted with diethyl ether, and the aqueous layer was separated. The organic extracts were washed with saturated sodium chloride, treated with anhydrous magnesium sulfate, filtered, and evaporated to afford N-benzyloxycarbonyl-L-tyrosine tert-butyl ester of sufficient purity for immediate conversion of the tyrosine hydroxyl into a carbamate. After the addition the aqueous layer was separated The organic extracts were washed with saturated sodium chloride treated with anhydrous magnesium sulfate filtered evaporated

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a 0° C. suspension of L-tyrosine tert-butyl ester (Bachem, 1.0. eq) and sodium bicarbonate (2.0 eq) in a 1:1 mixture of THF and water was added slowly with stirring benzyl chloroformate (1. 1 eq). After the addition, the mixture was stirred at 0° C. for 3 h and at room temperature for 24 h. The mixture was diluted with diethyl ether, and the aqueous layer was separated. The organic extracts were washed with saturated sodium chloride, treated with anhydrous magnesium sulfate, filtered, and evaporated to afford N-benzyloxycarbonyl-L-tyrosine tert-butyl ester of sufficient purity for immediate conversion of the tyrosine hydroxyl into a carbamate. After the addition the aqueous layer was separated The organic extracts were washed with saturated sodium chloride treated with anhydrous magnesium sulfate filtered evaporated

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a 0° C. suspension of L-tyrosine tert-butyl ester (Bachem, 1.0 eq) and sodium bicarbonate (2.0 eq) in a 1:1 mixture of THF and water was added slowly with stirring benzyl chloroformate (1.1 eq). After the addition, the mixture was stirred at 0° C. for 3 h and at room temperature for 24 h. The mixture was diluted with diethyl ether, and the aqueous layer was separated. The organic extracts were washed with saturated sodium chloride, treated with anhydrous magnesium sulfate, filtered, and evaporated to afford N-benzyloxycarbonyl-L-tyrosine tert-butyl ester of sufficient purity for immediate conversion of the tyrosine hydroxyl into a carbamate. After the addition the aqueous layer was separated The organic extracts were washed with saturated sodium chloride treated with anhydrous magnesium sulfate filtered evaporated

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a 0° C. suspension of L-tyrosine tert-butyl ester (Bachem, 1.0 eq) and sodium bicarbonate (2.0 eq) in a 1:1 mixture of THF and water was added slowly with stirring benzyl chloroformate (1.1 eq). After the addition, the mixture was stirred at 0° C. for 3 h and at room temperature for 24 h. The mixture was diluted with diethyl ether, and the aqueous layer was separated. The organic extracts were washed with saturated sodium chloride, treated with anhydrous magnesium sulfate, filtered, and evaporated to afford N-benzyloxycarbonyl-L-tyrosine tert-butyl ester of sufficient purity for immediate conversion of the tyrosine hydroxyl into a carbamate. After the addition the aqueous layer was separated The organic extracts were washed with saturated sodium chloride treated with anhydrous magnesium sulfate filtered evaporated

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a 0° C. suspension of L-tyrosine tert-butyl ester (Bachem, 1.0 eq) and sodium bicarbonate (2.0 eq) in a 1:1 mixture of THF and water was added slowly with stirring benzyl chloroformate (1.1 eq). After the addition, the mixture was stirred at 0° C. for 3 h and at room temperature for 24 h. The mixture was diluted with diethyl ether, and the aqueous layer was separated. The organic extracts were washed with saturated sodium chloride, treated with anhydrous magnesium sulfate, filtered, and evaporated to afford N-benzyloxycarbonyl-L-tyrosine tert-butyl ester of sufficient purity for immediate conversion of the tyrosine hydroxyl into a carbamate. After the addition the aqueous layer was separated The organic extracts were washed with saturated sodium chloride treated with anhydrous magnesium sulfate filtered evaporated

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

Procedure: Prepared using General Procedure 3: To a stirred solution of (S)-tert-butyl 2-(((benzyloxy)carbonyl)amino)-3-(4-hydroxyphenyl)propanoate (5.57 g, 15.0 mmol) and TEA (6.27 mL, 45.0 mmol) in DCM (15 mL) and acetonitrile (30 mL) was added 4-(heptyloxy)benzoyl chloride (3.78 mL, 15.75 mmol) dropwise. After stirring overnight, the mixture was quenched with saturated aqueous NaHCO3 (50 mL). The organic layer was dried over MgSO4, and concentrated. The product was purified by chromatography (EA/hexanes) to afford 8.19 g (93%) of (S)-4-(2-(((benzyloxy)carbonyl)amino)-3-(tert-butoxy)-3-oxopropyl)phenyl 4-(heptyloxy)benzoate INT-4. LCMS-ESI (m/z) calculated for C35H43NO7: 589; no mass ion observed, tR=5.26 min (Method 3). 1H NMR (400 MHz, CDCl3) δ 8.17-8.08 (m, 2H), 7.41-7.28 (m, 5H), 7.19 (d, J=8.4 Hz, 2H), 7.15-7.07 (m, 2H), 7.01-6.91 (m, 2H), 5.35-5.23 (m, 1H), 5.17-5.04 (m, 2H), 4.54 (dd, J=13.9, 6.1 Hz, 1H), 4.04 (t, J=6.6 Hz, 2H), 3.10 (d, J=5.9 Hz, 2H), 1.91-1.76 (m, 2H), 1.47 (ddd, J=15.2, 8.9, 6.7 Hz, 2H), 1.43-1.36 (m, 10H), 1.36-1.30 (m, 5H), 0.90 (t, J=6.9 Hz, 3H). Prepared the mixture was quenched with saturated aqueous NaHCO3 (50 mL) The organic layer was dried over MgSO4 concentrated The product was purified by chromatography (EA/hexanes)

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

Procedure: Prepared using General Procedure 3: To a stirred solution of (S)-tert-butyl 2-(((benzyloxy)carbonyl)amino)-3-(4-hydroxyphenyl)propanoate (5.57 g, 15.0 mmol) and TEA (6.27 mL, 45.0 mmol) in DCM (15 mL) and acetonitrile (30 mL) was added 4-(heptyloxy)benzoyl chloride (3.78 mL, 15.75 mmol) dropwise. After stirring overnight, the mixture was quenched with saturated aqueous NaHCO3 (50 mL). The organic layer was dried over MgSO4, and concentrated. The product was purified by chromatography (EA/hexanes) to afford 8.19 g (93%) of (S)-4-(2-(((benzyloxy)carbonyl)amino)-3-(tert-butoxy)-3-oxopropyl)phenyl 4-(heptyloxy)benzoate INT-4. LCMS-ESI (m/z) calculated for C35H43NO7: 589; no mass ion observed, tR=5.26 min (Method 3). 1H NMR (400 MHz, CDCl3) δ 8.17-8.08 (m, 2H), 7.41-7.28 (m, 5H), 7.19 (d, J=8.4 Hz, 2H), 7.15-7.07 (m, 2H), 7.01-6.91 (m, 2H), 5.35-5.23 (m, 1H), 5.17-5.04 (m, 2H), 4.54 (dd, J=13.9, 6.1 Hz, 1H), 4.04 (t, J=6.6 Hz, 2H), 3.10 (d, J=5.9 Hz, 2H), 1.91-1.76 (m, 2H), 1.47 (ddd, J=15.2, 8.9, 6.7 Hz, 2H), 1.43-1.36 (m, 10H), 1.36-1.30 (m, 5H), 0.90 (t, J=6.9 Hz, 3H). Prepared the mixture was quenched with saturated aqueous NaHCO3 (50 mL) The organic layer was dried over MgSO4 concentrated The product was purified by chromatography (EA/hexanes)