[(2R)-2-hydroxypropyl] benzoate

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

Procedure: To a solution of (2S)-2-[(tert-butoxy)carbonylamino]-3-[3,4-bis(phenylmethoxy)phenyl]propanoic acid (15.9 g, 33.3 mmol), (2R)-2-hydroxypropyl benzoate (5.0 g, 27.7 mmol), and 4-(dimethylamino)pyridine (340 mg) in 250 mL of anhydrous dichloromethane, 1-(3-dimethylaminopropyl)3-ethylcarbodiimide hydrochloride (EDAC) (8.0 g, 41.6 mmol) was slowly added. The resulting mixture was stirred at room temperature for 16 hrs. The reaction mixture was diluted with dichloromethane and washed with 0.5N HCl twice, followed by the addition of brine. The organic layer was separated, dried through a MgSO4 pad and concentrated under reduced pressure. Chromatography (silica gel, 1:5 then 1:4 ethyl acetate/hexane) of the residue followed by crystallization from 1:5 ethyl acetate/hexane afforded 8.0 g (45%) of the title compound. washed with 0.5N HCl twice followed by the addition of brine The organic layer was separated dried through a MgSO4 pad concentrated under reduced pressure Chromatography (silica gel, 1:5 then 1:4 ethyl acetate/hexane) of the residue followed by crystallization from 1:5 ethyl acetate/hexane

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

Procedure: To a solution of (2S)-2-[(tert-butoxy)carbonylamino]-3-[3,4-bis(phenylmethoxy)phenyl]propanoic acid (15.9 g, 33.3 mmol), (2R)-2-hydroxypropyl benzoate (5.0 g, 27.7 mmol), and 4-(dimethylamino)pyridine (340 mg) in 250 mL of anhydrous dichloromethane, 1-(3-dimethylaminopropyl)3-ethylcarbodiimide hydrochloride (EDAC) (8.0 g, 41.6 mmol) was slowly added. The resulting mixture was stirred at room temperature for 16 hrs. The reaction mixture was diluted with dichloromethane and washed with 0.5N HCl twice, followed by the addition of brine. The organic layer was separated, dried through a MgSO4 pad and concentrated under reduced pressure. Chromatography (silica gel, 1:5 then 1:4 ethyl acetate/hexane) of the residue followed by crystallization from 1:5 ethyl acetate/hexane afforded 8.0 g (45%) of the title compound. washed with 0.5N HCl twice followed by the addition of brine The organic layer was separated dried through a MgSO4 pad concentrated under reduced pressure Chromatography (silica gel, 1:5 then 1:4 ethyl acetate/hexane) of the residue followed by crystallization from 1:5 ethyl acetate/hexane

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

Procedure: To a solution of (2S)-2-[(tert-butoxy)carbonylamino]-3-[3,4-bis(phenylmethoxy)phenyl]propanoic acid (15.9 g, 33.3 mmol), (2R)-2-hydroxypropyl benzoate (5.0 g, 27.7 mmol), and 4-(dimethylamino)pyridine (340 mg) in 250 mL of anhydrous dichloromethane, 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDAC) (8.0 g, 41.6 mmol) was slowly added. The resulting mixture was stirred at room temperature for 16 hrs. The reaction mixture was diluted with dichloromethane and washed with 0.5N HCl twice, followed by the addition of brine. The organic layer was separated, dried through a MgSO4 pad and concentrated under reduced pressure. Chromatography (silica gel, 1:5 then 1:4 ethyl acetate/hexane) of the residue followed by crystallization from 1:5 ethyl acetate/hexane afforded 8.0 g (45%) of the title compound. washed with 0.5N HCl twice followed by the addition of brine The organic layer was separated dried through a MgSO4 pad concentrated under reduced pressure Chromatography (silica gel, 1:5 then 1:4 ethyl acetate/hexane) of the residue followed by crystallization from 1:5 ethyl acetate/hexane

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

Procedure: To a solution of (2S)-2-[(tert-butoxy)carbonylamino]-3-[3,4-bis(phenylmethoxy)phenyl]propanoic acid (15.9 g, 33.3 mmol), (2R)-2-hydroxypropyl benzoate (5.0 g, 27.7 mmol), and 4-(dimethylamino)pyridine (340 mg) in 250 mL of anhydrous dichloromethane, 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDAC) (8.0 g, 41.6 mmol) was slowly added. The resulting mixture was stirred at room temperature for 16 hrs. The reaction mixture was diluted with dichloromethane and washed with 0.5N HCl twice, followed by the addition of brine. The organic layer was separated, dried through a MgSO4 pad and concentrated under reduced pressure. Chromatography (silica gel, 1:5 then 1:4 ethyl acetate/hexane) of the residue followed by crystallization from 1:5 ethyl acetate/hexane afforded 8.0 g (45%) of the title compound. washed with 0.5N HCl twice followed by the addition of brine The organic layer was separated dried through a MgSO4 pad concentrated under reduced pressure Chromatography (silica gel, 1:5 then 1:4 ethyl acetate/hexane) of the residue followed by crystallization from 1:5 ethyl acetate/hexane

Conditions: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Benzoyl chloride (10.98 mL, 94.62 mmol) was added dropwise to a solution of (R)-(−)-1,2-propanediol (6.00 g, 78.85 mmol) and 2,4,6-collidine (7.22 mL, 54.67 mmol) in 100 mL of anhydrous dichloromethane at −78° C. The reaction was stirred at −78° C. for three hours and at room temperature for 1 hr, before quenching with water (10 mL) for 15 minutes. The quenched mixture was washed with 0.5N HCl (4×50 mL) until the dark color diminished, and then with saturated NaHCO3 solution (4×50 mL) and brine. The organic layer was separated, dried over Na2SO4 and concentrated. Chromatography (silica gel 230-400 Mesh, 1:9 ethyl acetate/Hexane) of the residue afforded 8.9 g (63%) of (2R)-2-Hydroxypropyl benzoate as a white solid. 1H NMR (400 MHz, DMSO-d6): δ 1.13 (d, J=6.4 Hz, 3H), 3.93 (m, 1H), 4.10 (m, 2H), 4.95 (d, J=4.8 Hz, 1H), 7.51 (t, J=7.2 Hz, 2H), 7.64 (t, J=7.6 Hz, 1H), 7.99 (d, J=6.8 Hz, 2H); MS (ESI) m/z 181 (M+H)+. before quenching with water (10 mL) for 15 minutes The quenched mixture was washed with 0.5N HCl (4×50 mL) until the dark color The organic layer was separated dried over Na2SO4 concentrated

Conditions: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Benzoyl chloride (10.98 mL, 94.62 mmol) was added dropwise to a solution of (R)-(−)-1,2-propanediol (6.00 g, 78.85 mmol) and 2,4,6-collidine (7.22 mL, 54.67 mmol) in 100 mL of anhydrous dichloromethane at −78° C. The reaction was stirred at −78° C. for three hours and at room temperature for 1 hr, before quenching with water (10 mL) for 15 minutes. The quenched mixture was washed with 0.5N HCl (4×50 mL) until the dark color diminished, and then with saturated NaHCO3 solution (4×50 mL) and brine. The organic layer was separated, dried over Na2SO4 and concentrated. Chromatography (silica gel 230-400 Mesh, 1:9 ethyl acetate/Hexane) of the residue afforded 8.9 g (63%) of (2R)-2-Hydroxypropyl benzoate as a white solid. 1H NMR (400 MHz, DMSO-d6): δ 1.13 (d, J=6.4 Hz, 3H), 3.93 (m, 1H), 4.10 (m, 2H), 4.95 (d, J=4.8 Hz, 1H), 7.51 (t, J=7.2 Hz, 2H), 7.64 (t, J=7.6 Hz, 1H), 7.99 (d, J=6.8 Hz, 2H); MS (ESI) m/z 181 (M+H)+. before quenching with water (10 mL) for 15 minutes The quenched mixture was washed with 0.5N HCl (4×50 mL) until the dark color The organic layer was separated dried over Na2SO4 concentrated

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

Procedure: To a solution of (2S)-2-[(tert-butoxy)carbonylamino]-3-[3,4-bis(phenylmethoxy)phenyl]propanoic acid (15.9 g, 33.3 mmol), (2R)-2-hydroxypropyl benzoate (5.0 g, 27.7 mmol), and 4-(dimethylamino)pyridine (340 mg) in 250 mL of anhydrous dichloromethane, 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDAC) (8.0 g, 41.6 mmol) was slowly added. The resulting mixture was stirred at room temperature for 16 hrs. The reaction mixture was diluted with dichloromethane and washed with 0.5N HCl twice, followed by the addition of brine. The organic layer was separated, dried through a MgSO4 pad and concentrated under reduced pressure. Chromatography (silica gel, 1:5 then 1:4 ethyl acetate/hexane) of the residue followed by crystallization from 1:5 ethyl acetate/hexane afforded 8.0 g (45%) of the title compound. washed with 0.5N HCl twice followed by the addition of brine The organic layer was separated dried through a MgSO4 pad concentrated under reduced pressure Chromatography (silica gel, 1:5 then 1:4 ethyl acetate/hexane) of the residue followed by crystallization from 1:5 ethyl acetate/hexane

Conditions: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Benzoyl chloride (10.98 mL, 94.62 mmol) was added dropwise to a solution of (R)-(−)-1,2-propanediol (6.00 g, 78.85 mmol) and 2,4,6-collidine (7.22 mL, 54.67 mmol) in 100 mL of anhydrous dichloromethane at −78° C. The reaction was stirred at −78° C. for three hours and at room temperature for 1 hr, before quenching with water (10 mL) for 15 minutes. The quenched mixture was washed with 0.5N HCl (4×50 mL) until the dark color diminished, and then with saturated NaHCO3 solution (4×50 mL) and brine. The organic layer was separated, dried over Na2SO4 and concentrated. Chromatography (silica gel 230-400 Mesh, 1:9 ethyl acetate/Hexane) of the residue afforded 8.9 g (63%) of (2R)-2-Hydroxypropyl benzoate as a white solid. 1H NMR (400 MHz, DMSO-d6): δ 1.13 (d, J=6.4 Hz, 3H), 3.93 (m, 1H), 4.10 (m, 2H), 4.95 (d, J=4.8 Hz, 1H), 7.51 (t, J=7.2 Hz, 2H), 7.64 (t, J=7.6 Hz, 1H), 7.99 (d, J=6.8 Hz, 2H); MS (ESI) m/z 181 (M+H)+. before quenching with water (10 mL) for 15 minutes The quenched mixture was washed with 0.5N HCl (4×50 mL) until the dark color The organic layer was separated dried over Na2SO4 concentrated

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

Procedure: To a solution of (2S)-2-[(tert-butoxy)carbonylamino]-3-[3,4-bis(phenylmethoxy)phenyl]propanoic acid (15.9 g, 33.3 mmol), (2R)-2-hydroxypropyl benzoate (5.0 g, 27.7 mmol), and 4-(dimethylamino)pyridine (340 mg) in 250 mL of anhydrous dichloromethane, 1-(3-dimethylaminopropyl)3-ethylcarbodiimide hydrochloride (EDAC) (8.0 g, 41.6 mmol) was slowly added. The resulting mixture was stirred at room temperature for 16 hrs. The reaction mixture was diluted with dichloromethane and washed with 0.5N HCl twice, followed by the addition of brine. The organic layer was separated, dried through a MgSO4 pad and concentrated under reduced pressure. Chromatography (silica gel, 1:5 then 1:4 ethyl acetate/hexane) of the residue followed by crystallization from 1:5 ethyl acetate/hexane afforded 8.0 g (45%) of the title compound. washed with 0.5N HCl twice followed by the addition of brine The organic layer was separated dried through a MgSO4 pad concentrated under reduced pressure Chromatography (silica gel, 1:5 then 1:4 ethyl acetate/hexane) of the residue followed by crystallization from 1:5 ethyl acetate/hexane

Conditions: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Benzoyl chloride (10.98 mL, 94.62 mmol) was added dropwise to a solution of (R)-(−)-1,2-propanediol (6.00 g, 78.85 mmol) and 2,4,6-collidine (7.22 mL, 54.67 mmol) in 100 mL of anhydrous dichloromethane at −78° C. The reaction was stirred at −78° C. for three hours and at room temperature for 1 hr, before quenching with water (10 mL) for 15 minutes. The quenched mixture was washed with 0.5N HCl (4×50 mL) until the dark color diminished, and then with saturated NaHCO3 solution (4×50 mL) and brine. The organic layer was separated, dried over Na2SO4 and concentrated. Chromatography (silica gel 230-400 Mesh, 1:9 ethyl acetate/Hexane) of the residue afforded 8.9 g (63%) of (2R)-2-Hydroxypropyl benzoate as a white solid. 1H NMR (400 MHz, DMSO-d6): δ 1.13 (d, J=6.4 Hz, 3H), 3.93 (m, 1H), 4.10 (m, 2H), 4.95 (d, J=4.8 Hz, 1H), 7.51 (t, J=7.2 Hz, 2H), 7.64 (t, J=7.6 Hz, 1H), 7.99 (d, J=6.8 Hz, 2H); MS (ESI) m/z 181 (M+H)+. before quenching with water (10 mL) for 15 minutes The quenched mixture was washed with 0.5N HCl (4×50 mL) until the dark color The organic layer was separated dried over Na2SO4 concentrated

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

Procedure: To a solution of (2S)-2-[(tert-butoxy)carbonylamino]-3-[3,4-bis(phenylmethoxy)phenyl]propanoic acid (15.9 g, 33.3 mmol), (2R)-2-hydroxypropyl benzoate (5.0 g, 27.7 mmol), and 4-(dimethylamino)pyridine (340 mg) in 250 mL of anhydrous dichloromethane, 1-(3-dimethylaminopropyl)3-ethylcarbodiimide hydrochloride (EDAC) (8.0 g, 41.6 mmol) was slowly added. The resulting mixture was stirred at room temperature for 16 hrs. The reaction mixture was diluted with dichloromethane and washed with 0.5N HCl twice, followed by the addition of brine. The organic layer was separated, dried through a MgSO4 pad and concentrated under reduced pressure. Chromatography (silica gel, 1:5 then 1:4 ethyl acetate/hexane) of the residue followed by crystallization from 1:5 ethyl acetate/hexane afforded 8.0 g (45%) of the title compound. washed with 0.5N HCl twice followed by the addition of brine The organic layer was separated dried through a MgSO4 pad concentrated under reduced pressure Chromatography (silica gel, 1:5 then 1:4 ethyl acetate/hexane) of the residue followed by crystallization from 1:5 ethyl acetate/hexane