tert-butyl N-(3-hydroxy-1-phenylpropyl)carbamate

Conditions: temp:0.00; pressure:0.00; stir:

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

Procedure: To a solution of 1.63 g of tert-butyl 3-hydroxy-1-phenylpropylcarbamate (Formula 11) in 15 mL of dimethyl sulfoxide (DMSO) was added 2.72 mL of triethylamine. The solution was cooled to 0° C. and 3.1 g of sulfur trioxide pyridine complex in 15 mL of DMSO was added. The reaction mixture was stirred at room temperature for 1 hour then poured onto ice-water and extracted with ethyl acetate. The combined ethyl acetate layers were washed with 10% acetic acid, water, 5% sodium bicarbonate, and brine, dried over sodium sulfate and concentrated. Column chromatography (40% ethyl acetate/hexane) gave 1.2 g (74%) of tert-butyl-3-oxo-1-phenylpropylcarbamate (Formula 12) as a white solid. 1H NMR (300 MHz, CDCl3) δ 1.43 (s, 9H), 2.89-2.96 (m, 2H), 5.23 (br, 1H), 5.32 (br, 1H), 7.27-7.37 (m, 5H), 9.74 (m, 1H). then poured onto ice-water extracted with ethyl acetate The combined ethyl acetate layers were washed with 10% acetic acid, water, 5% sodium bicarbonate, and brine dried over sodium sulfate concentrated

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

Procedure: To a solution of 1.63 g of tert-butyl 3-hydroxy-1-phenylpropylcarbamate (Formula 11) in 15 mL of dimethyl sulfoxide (DMSO) was added 2.72 mL of triethylamine. The solution was cooled to 0° C. and 3.1 g of sulfur trioxide pyridine complex in 15 mL of DMSO was added. The reaction mixture was stirred at room temperature for 1 hour then poured onto ice-water and extracted with ethyl acetate. The combined ethyl acetate layers were washed with 10% acetic acid, water, 5% sodium bicarbonate, and brine, dried over sodium sulfate and concentrated. Column chromatography (40% ethyl acetate/hexane) gave 1.2 g (74%) of tert-butyl-3-oxo-1-phenylpropylcarbamate (Formula 12) as a white solid. 1H NMR (300 MHz, CDCl3) δ 1.43 (s, 9H), 2.89-2.96 (m, 2H), 5.23 (br, 1H), 5.32 (br, 1H), 7.27-7.37 (m, 5H), 9.74 (m, 1H). then poured onto ice-water extracted with ethyl acetate The combined ethyl acetate layers were washed with 10% acetic acid, water, 5% sodium bicarbonate, and brine dried over sodium sulfate concentrated

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

Procedure: To a 17.9 mmol suspension of 3-(tert-butoxycarbonylamino)-3-phenylpropanoic acid (Formula 10) in tetrahydrofuran (THF) at 0° C. was added 2.74 mL of triethyl amine and 1.52 mL of methyl chloroformate. The mixture was stirred at 0° C. for 15 minutes. Next, the white solid formed was filtered off and washed with 10 mL of THF. The filtrate was added drop-wise to 8.4 mL of 26.8 mmol sodium borohydride at 0° C. and stirred for 30 min. The mixture was then stirred at room temperature for 2 hr. Ten percent hydrochloric acid (HCl) was added until a pH of 2 was reached, and then was extracted using ethyl acetate. The resulting combined ethyl acetate layers were washed with sodium carbonate, water, brine, and concentrated. Column chromatography (50% ethyl acetate/hexane) gave 1.63 g (36%) of the title compound as a colorless oil. The aqueous phase was acidified with HCl and extracted with ethyl acetate to recover 2 g of 3-(tert-butoxycarbonylamino)-3-phenylpropanoic acid. 1H NMR (300 MHz, CDCl3) δ 1.45 (s, 9H), 1.62-1.63 (m, 1H), 1.79-1.87 (m, 1H), 3.68-3.74 (m, 2H), 5.23 (br, 1H), 5.32 (br, 1H), 7.26-7.38 (m, 5H). Next, the white solid formed was filtered off washed with 10 mL of THF stirred for 30 min The mixture was then stirred at room temperature for 2 hr was extracted were washed with sodium carbonate, water, brine concentrated

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

Procedure: To a solution of 1.63 g of tert-butyl 3-hydroxy-1-phenylpropylcarbamate (Formula 11) in 15 mL of dimethyl sulfoxide (DMSO) was added 2.72 mL of triethylamine. The solution was cooled to 0° C. and 3.1 g of sulfur trioxide pyridine complex in 15 mL of DMSO was added. The reaction mixture was stirred at room temperature for 1 hour then poured onto ice-water and extracted with ethyl acetate. The combined ethyl acetate layers were washed with 10% acetic acid, water, 5% sodium bicarbonate, and brine, dried over sodium sulfate and concentrated. Column chromatography (40% ethyl acetate/hexane) gave 1.2 g (74%) of tert-butyl-3-oxo-1-phenylpropylcarbamate (Formula 12) as a white solid. 1H NMR (300 MHz, CDCl3) δ 1.43 (s, 9H), 2.89-2.96 (m, 2H), 5.23 (br, 1H), 5.32 (br, 1H), 7.27-7.37 (m, 5H), 9.74 (m, 1H). then poured onto ice-water extracted with ethyl acetate The combined ethyl acetate layers were washed with 10% acetic acid, water, 5% sodium bicarbonate, and brine dried over sodium sulfate concentrated

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

Procedure: To a 17.9 mmol suspension of 3-(tert-butoxycarbonylamino)-3-phenylpropanoic acid (Formula 10) in tetrahydrofuran (THF) at 0° C. was added 2.74 mL of triethyl amine and 1.52 mL of methyl chloroformate. The mixture was stirred at 0° C. for 15 minutes. Next, the white solid formed was filtered off and washed with 10 mL of THF. The filtrate was added drop-wise to 8.4 mL of 26.8 mmol sodium borohydride at 0° C. and stirred for 30 min. The mixture was then stirred at room temperature for 2 hr. Ten percent hydrochloric acid (HCl) was added until a pH of 2 was reached, and then was extracted using ethyl acetate. The resulting combined ethyl acetate layers were washed with sodium carbonate, water, brine, and concentrated. Column chromatography (50% ethyl acetate/hexane) gave 1.63 g (36%) of the title compound as a colorless oil. The aqueous phase was acidified with HCl and extracted with ethyl acetate to recover 2 g of 3-(tert-butoxycarbonylamino)-3-phenylpropanoic acid. 1H NMR (300 MHz, CDCl3) δ 1.45 (s, 9H), 1.62-1.63 (m, 1H), 1.79-1.87 (m, 1H), 3.68-3.74 (m, 2H), 5.23 (br, 1H), 5.32 (br, 1H), 7.26-7.38 (m, 5H). Next, the white solid formed was filtered off washed with 10 mL of THF stirred for 30 min The mixture was then stirred at room temperature for 2 hr was extracted were washed with sodium carbonate, water, brine concentrated