tert-butyl (2S)-2-(9H-fluoren-9-ylmethoxycarbonylamino)-3-(4-hydroxyphenyl)propanoate

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

Procedure: In a manner similar to that described in Example H, the product from Example G (0.50 g, 1.08 mmol) and BOC-3-aminobenzylalcohol (0.24 g, 1.08 mmol) were converted to the title compound (0.40 g, 60%).

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

Procedure: In a manner similar to that described in Example H, the product from Example G (0.50 g, 1.08 mmol) and BOC-3-aminobenzylalcohol (0.24 g, 1.08 mmol) were converted to the title compound (0.40 g, 60%).

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

Procedure: A solution of the product from Example G (1.0 g, 2.18 mmol) was dissolved in DMF and cooled to 0° C. The resulting solution treated with NaH (2.18 mmol) and was stirred for 1 hour at 0° C. and treated with α-bromo-p-tolunitrile (0.45 g, 2.30 mmol). The reaction mixture was warmed to room temperature and stirred overnight. The reaction mixture was poured into a separatory funnel containing ethyl acetate (50 mL) and water (50 mL) and shaken. The organic phase was separated and washed with brine, dried, and concentrated to give the title compound (0.76 g, 61%). The reaction mixture was warmed to room temperature stirred overnight The reaction mixture was poured into a separatory funnel shaken The organic phase was separated washed with brine dried concentrated

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

Procedure: In a manner similar to that described in Example H, the product from Example G (0.5 g, 1.08 mmol) and 4-pyridylcarbinol (0.12 mL, 1.26 mmol) were converted to the title compound.

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

Procedure: In a manner similar to that described in Example H, the product from Example G ((S)-2-(9H-fluoren-9-ylmethoxycarbonylamino)-3-(4-hydroxyphenyl)-propionic acid tert-butyl ester) (4.39 g, 9.50 mmol) and 3-pyridylcarbinol (0.92 mL, 9.50 mmol) were converted to the title compound.

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

Procedure: In a manner similar to that described in Example H, the product from Example G ((S)-2-(9H-fluoren-9-ylmethoxycarbonylamino)-3-(4-hydroxyphenyl)-propionic acid tert-butyl ester) (4.39 g, 9.50 mmol) and 3-pyridylcarbinol (0.92 mL, 9.50 mmol) were converted to the title compound.

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

Procedure: In a manner similar to that described in Example H, the product from Example G ((S)-2-(9H-fluoren-9-ylmethoxycarbonylamino)-3-(4-hydroxyphenyl)-propionic acid tert-butyl ester) (4.39 g, 9.50 mmol) and 3-pyridylcarbinol (0.92 mL, 9.50 mmol) were converted to the title compound.

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

Procedure: The product from Example G ((S)-2-(9H-fluoren-9-ylmethoxycarbonylamino)-3-(4-hydroxyphenyl)-propionic acid tert-butyl ester) (4.00 g, 8.64 mmol), 2-pyridylcarbinol (0.92 mL, 9.50 mmol) and triphenylphosphine (2.24 g, 8.64 mmol) were dissolved in 50 mL of dry THF. The solution was cooled in an ice bath under an argon atmosphere and diethyl azidocarboxylate (1.36 mL, 8.64 mmol) was added dropwise over 20 minutes. The ice bath was removed and the solution allowed to stir overnight at room temperature. The solution was concentrated under reduced pressure and partitioned between ethyl acetate and water (100 mL each) and separated. The organic layer was washed with 10% aqueous HCl (2×50 mL), 10% sodium bicarbonate (2×50 mL), brine (2×50 mL), dried with magnesium sulfate, filtered, and concentrated under reduced pressure to a foam (4.80 g). The foam was purified by chromatography (silica gel, 1:1.5 ethyl acetate/hexane) to give the product as a white foam (3.90 g, 82%). The solution was cooled in an ice bath under an argon atmosphere The ice bath was removed The solution was concentrated under reduced pressure partitioned between ethyl acetate and water (100 mL each) separated The organic layer was washed with 10% aqueous HCl (2×50 mL), 10% sodium bicarbonate (2×50 mL), brine (2×50 mL) dried with magnesium sulfate filtered concentrated under reduced pressure to a foam (4.80 g) The foam was purified by chromatography (silica gel, 1:1.5 ethyl acetate/hexane)

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

Procedure: A solution of -tyrosine t-butyl ester (Bachem, 20.0 g, 84.3 mmol) and FMOC-OSu (Bachem, 24.68 g, 71.2 mmol) was dissolved in 400 mL of dioxane and 400 mL of water. The pH of the resulting solution was adjusted to pH=9 and the solution stirred overnight at room temperature. The reaction mixture was concentrated to ½ volume and treated with concentrated HCl until the pH=5. The resulting solution was extracted with ethyl acetate (5×150 mL), the combined organic extracts were dried with MgSO4 and concentrated. The residue was crystallized from hot heptane/EtOAc. The solid that formed was collected by filtration and air dried to give the title compound (28.5 g, 87%) as a white solid. The reaction mixture was concentrated treated with concentrated HCl until the pH=5 The resulting solution was extracted with ethyl acetate (5×150 mL) the combined organic extracts were dried with MgSO4 concentrated The residue was crystallized from hot heptane/EtOAc The solid that formed was collected by filtration and air dried