methyl (4S)-5-hydroxy-4-[(2-methylpropan-2-yl)oxycarbonylamino]pentanoate

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

Procedure: Methyl (4S)-4-[(tert-butoxy)carbonylamino]-5-hydroxypentanoate (9.11 mmol, 2.25 g) was dissolved in 30 mL of methylene chloride. p-Toluenesulfonyl chloride (9.1 mmol, 1.7 g) and triethylamine (27.33 mmol, 3.8 mL) were added and the reaction was stirred at room temperature overnight. Solvent was removed in vacuo and crude was purified by column chromatography (SiO2, 4:1 n-hexanes/ethyl acetate to 7:3 n-hexanes/ethyl acetate) to yield the title compound (1.98 g, 54% yield). ES-MS: 402 (M+1). Solvent was removed in vacuo and crude was purified by column chromatography (SiO2, 4:1 n-hexanes/ethyl acetate to 7:3 n-hexanes/ethyl acetate)

Conditions: temp:-10.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: In a round-bottom flask, (2S)-2-[(tert-butoxy)carbonylamino]-4-(methoxycarbonyl)butanoic acid (78 mmol, 20.36 g) was dissolved in THF (300 mL). The solution was cooled to −10° C. and N-methylmorpholine (78 mmol, 8.58 mL) and ethyl chloroformate (78 mmol, 7.48 mL) were added, followed by sodium borohydride (234 mmol, 8.85 g). The reaction was stirred for 30 min at this temperature and then quenched by slow addition of saturated solution of ammonium chloride until no further evolution of hydrogen was observed. The reaction mixture was then extracted with ethyl acetate and dried over magnesium sulfate. After filtration, solvent was evaporated and the crude material was purified by column chromatography (SiO2, 1:1 n-hexanes/ethyl acetate) to yield the title compound (11.68 g, 61% yield). ES-MS: 248 (M+1). quenched by slow addition of saturated solution of ammonium chloride until no further evolution of hydrogen The reaction mixture was then extracted with ethyl acetate dried over magnesium sulfate After filtration, solvent was evaporated the crude material was purified by column chromatography (SiO2, 1:1 n-hexanes/ethyl acetate)

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

Procedure: 120 ml of isopropenyl methyl ether are added to a solution of 159.5 g of methyl 4(S)-tert-butoxycarbonylamino-5-hydroxyvalerate and 3 g of p-toluenesulfonic acid hydrate in 500 ml of methylene chloride at 0° C. The reaction mixture is stirred at 0° C. for 2 h and at room temperature for 3 h. The reaction solution is washed with 100 ml of saturated sodium bicarbonate solution and evaporated. The title compound is obtained by FC (800 g of silica gel, mobile phase E): [α]D =+20.5 (c=0.8 in CHCl3); Rf (D)=0.24; MS: (M)+ =287. The reaction solution is washed with 100 ml of saturated sodium bicarbonate solution evaporated

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

Procedure: Methyl (4S)-4-[(tert-butoxy)carbonylamino]-5-hydroxypentanoate (9.11 mmol, 2.25 g) was dissolved in 30 mL of methylene chloride. p-Toluenesulfonyl chloride (9.1 mmol, 1.7 g) and triethylamine (27.33 mmol, 3.8 mL) were added and the reaction was stirred at room temperature overnight. Solvent was removed in vacuo and crude was purified by column chromatography (SiO2, 4:1 n-hexanes/ethyl acetate to 7:3 n-hexanes/ethyl acetate) to yield the title compound (1.98 g, 54% yield). ES-MS: 402 (M+1). Solvent was removed in vacuo and crude was purified by column chromatography (SiO2, 4:1 n-hexanes/ethyl acetate to 7:3 n-hexanes/ethyl acetate)

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

Procedure: Methyl (4S)-4-[(tert-butoxy)carbonylamino]-5-hydroxypentanoate (9.11 mmol, 2.25 g) was dissolved in 30 mL of methylene chloride. p-Toluenesulfonyl chloride (9.1 mmol, 1.7 g) and triethylamine (27.33 mmol, 3.8 mL) were added and the reaction was stirred at room temperature overnight. Solvent was removed in vacuo and crude was purified by column chromatography (SiO2, 4:1 n-hexanes/ethyl acetate to 7:3 n-hexanes/ethyl acetate) to yield the title compound (1.98 g, 54% yield). ES-MS: 402 (M+1). Solvent was removed in vacuo and crude was purified by column chromatography (SiO2, 4:1 n-hexanes/ethyl acetate to 7:3 n-hexanes/ethyl acetate)

Conditions: temp:-10.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: In a round-bottom flask, (2S)-2-[(tert-butoxy)carbonylamino]-4-(methoxycarbonyl)butanoic acid (78 mmol, 20.36 g) was dissolved in THF (300 mL). The solution was cooled to −10° C. and N-methylmorpholine (78 mmol, 8.58 mL) and ethyl chloroformate (78 mmol, 7.48 mL) were added, followed by sodium borohydride (234 mmol, 8.85 g). The reaction was stirred for 30 min at this temperature and then quenched by slow addition of saturated solution of ammonium chloride until no further evolution of hydrogen was observed. The reaction mixture was then extracted with ethyl acetate and dried over magnesium sulfate. After filtration, solvent was evaporated and the crude material was purified by column chromatography (SiO2, 1:1 n-hexanes/ethyl acetate) to yield the title compound (11.68 g, 61% yield). ES-MS: 248 (M+1). quenched by slow addition of saturated solution of ammonium chloride until no further evolution of hydrogen The reaction mixture was then extracted with ethyl acetate dried over magnesium sulfate After filtration, solvent was evaporated the crude material was purified by column chromatography (SiO2, 1:1 n-hexanes/ethyl acetate)

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

Procedure: (S)-methyl 4-(tert-butoxycarbonylamino)-5-hydroxypentanoate (24 g, 97.2 mmol) and isopropenyl methyl ether (88.8 g, 854.6 mmol) was dissolved in acetone (2000 mL) and BF3.Et2O (0.82 mL, 5.84 mmol) was added at rt. The mixture was stirred for 1 hr at rt. The reaction was quenched by addition of Et3N (11.6 mL). The reaction solution was washed with aqueous saturated NaHCO3 (200 mL) and evaporated, and (S)-tert-butyl 4-(3-methoxy-3-oxopropyl)-2,2-dimethyloxazolidine-3-carboxylate (25.1 g, 90%) was obtained as an oil, which was used in the next step without further purification. The reaction was quenched by addition of Et3N (11.6 mL) The reaction solution was washed with aqueous saturated NaHCO3 (200 mL) evaporated

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

Procedure: To a stirred solution of (S)-2-(tert-butoxycarbonylamino)-5-methoxy-5-oxopentanoic acid (35.2 g, 0.135 mol) in THF (500 mL) at −10° C. was added N-methylmorpholine (15 mL, 0.135 mol) followed by ethyl chloroformate (14.72 g, 0.135 mol). After 10 min, NaBH4 (15.37 g, 0.405 mol) was added in one portion. MeOH (1200 mL) was then added dropwise to the mixture over a period of 20 min at 0° C. The solution was stirred for an additional 20 min and then neutralized with 1M KHSO4. The organic solvent was removed and the aqueous layer was extracted with EtOAc (3×500 ml). The combined organic phases were washed consecutively with 1M KHSO4 (300 mL), H2O (300 mL), 5% aqueous NaHCO3 (300 mL), and dried (Na2SO4). The solvent was evaporated to give a residue, which was purified by column chromatography to give the desired (S)-methyl 4-(tert-butoxycarbonylamino)-5-hydroxypentanoate (24 g, 72%) The organic solvent was removed the aqueous layer was extracted with EtOAc (3×500 ml) The combined organic phases were washed consecutively with 1M KHSO4 (300 mL), H2O (300 mL), 5% aqueous NaHCO3 (300 mL) dried (Na2SO4) The solvent was evaporated to give a residue, which was purified by column chromatography

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

Procedure: (S)-methyl 4-(tert-butoxycarbonylamino)-5-hydroxypentanoate (12 g, 48.6 mmol) and isopropenyl methyl ether (44.4 g, 427.3 mmol) was dissolved in acetone (200 mL) and BF3.Et2O (0.41 mL, 2.92 mmol) was added at rt and stirred for 1 hour. The reaction was stopped by addition of Et3N (5.8 mL). The reaction solution was washed with 100 mL of saturated NaHCO3 and evaporated, and (S)-tert-butyl 4-(3-methoxy-3-oxopropyl)-2,2-dimethyloxazolidine-3-carboxylate (10 g, yield 72%) was obtained as an oil that was used in the next step without further purification. The reaction solution was washed with 100 mL of saturated NaHCO3 evaporated

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

Procedure: To a solution (S)-2-(tert-butoxycarbonylamino)-5-methoxy-5-oxopentanoic acid (26.1 g, 0.1 mol) in THF (500 mL), BH3.Me2S (80 mL, 0.8 mmol) was added dropwise at −78° C., then stirred at rt for 3 hrs. The reaction was stopped by careful addition of methanol. After evaporation and three distillations of methanol, the residue was dissolved in EtOAc, washed with 1 M NaHCO3, and brine. (S)-methyl 4-(tert-butoxycarbonylamino)-5-hydroxypentanoate (12 g, yield 49%) was obtained as an oil that was used in the next step without further purification. After evaporation and three distillations of methanol the residue was dissolved in EtOAc washed with 1 M NaHCO3, and brine

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

Procedure: (S)-Methyl 4-(tert-butoxycarbonylamino)-5-hydroxypentanoate (24 g, 97.2 mmol) and isopropenyl methyl ether (88.8 g, 854.6 mmol) was dissolved in acetone (2000 mL) and BF3.Et2O (0.82 mL, 5.84 mmol) was added at rt. The mixture was stirred for 1 hr at rt. The reaction was quenched by addition of Et3N (11.6 mL). The reaction solution was washed with aqueous saturated NaHCO3 (200 mL) and evaporated, and (S)-tert-butyl 4-(3-methoxy-3-oxopropyl)-2,2-dimethyloxazolidine-3-carboxylate (25.1 g, 90%) was obtained as an oil, which was used in the next step without further purification. The reaction was quenched by addition of Et3N (11.6 mL) The reaction solution was washed with aqueous saturated NaHCO3 (200 mL) evaporated

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

Procedure: (S)-Methyl 4-(tert-butoxycarbonylamino)-5-hydroxypentanoate (24 g, 97.2 mmol) and isopropenyl methyl ether (88.8 g, 854.6 mmol) was dissolved in acetone (2000 mL) and BF3.Et2O (0.82 mL, 5.84 mmol) was added at rt. The mixture was stirred for 1 hr at rt. The reaction was quenched by addition of Et3N (11.6 mL). The reaction solution was washed with aqueous saturated NaHCO3 (200 mL) and evaporated, and (S)-tert-butyl 4-(3-methoxy-3-oxopropyl)-2,2-dimethyloxazolidine-3-carboxylate (25.1 g, 90%) was obtained as an oil, which was used in the next step without further purification. The reaction was quenched by addition of Et3N (11.6 mL) The reaction solution was washed with aqueous saturated NaHCO3 (200 mL) evaporated