benzyl (2S)-4-hydroxy-2-[(2-methylpropan-2-yl)oxycarbonylamino]butanoate

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

Procedure: N-t-Boc-L-homoserine (5.14 g, 23.45 mmol) and potassium bicarbonate (2.46 g, 24.6 mmol) was weighed out in a round bottom flask and to it was added anhydrous N,N-dimethylformamide (100 mL) and benzyl bromide (4.2 g, 24.6 mmol). The mixture was stirred at room temperature for 18 hours. The crude mixture was then diluted with ethyl acetate and washed, respectively, with brine, saturated NaHCO3 and brine, and dried over Na2SO4. The organic layer was then concentrated down on rotovap and purified on normal phase column chromatography. Yield=7.27 g (100%). washed respectively, with brine, saturated NaHCO3 and brine, and dried over Na2SO4 The organic layer was then concentrated down on rotovap purified on normal phase column chromatography

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

Procedure: N-t-Boc-L-homoserine (5.14 g, 23.45 mmol) and potassium bicarbonate (2.46 g, 24.6 mmol) was weighed out in a round bottom flask and to it was added anhydrous N,N-dimethylformamide (100 mL) and benzyl bromide (4.2 g, 24.6 mmol). The mixture was stirred at room temperature for 18 hours. The crude mixture was then diluted with ethyl acetate and washed, respectively, with brine, saturated NaHCO3 and brine, and dried over Na2SO4. The organic layer was then concentrated down on rotovap and purified on normal phase column chromatography. Yield=7.27 g (100%). washed respectively, with brine, saturated NaHCO3 and brine, and dried over Na2SO4 The organic layer was then concentrated down on rotovap purified on normal phase column chromatography

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

Procedure: (S)-Benzyl 2-(tert-butoxycarbonylamino)-4-hydroxybutanoate (5.76 g, 18.62 mmol) and 1,3-benzodithiol-2-ylium tetrafluoroborate (4.69 g, 19.55 mmol) were dissolved in dichloromethane (186 mL) and pyridine (4.42 g, 55.86 mmol) was added at room temperature. The mixture was stirred overnight. Upon completion of the reaction, it was quenched with triethylamine (11.5 g, 113.5 mmol) and diluted with dichloromethane. The organic layer was then washed with saturated NaHCO3 and brine. The organic layer was dried over MgSO4 and concentrated down in vacuo. The residue was then purified on normal phase column to obtain a clear oil. 7.6 g (88%). Upon completion of the reaction, it The organic layer was then washed with saturated NaHCO3 and brine The organic layer was dried over MgSO4 concentrated down in vacuo The residue was then purified on normal phase column to obtain a clear oil

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

Procedure: N-t-Boc-L-homoserine (5.14 g, 23.45 mmol) and potassium bicarbonate (2.46 g, 24.6 mmol) was weighed out in a round bottom flask and to it was added anhydrous N,N-dimethylformamide (100 mL) and benzyl bromide (4.2 g, 24.6 mmol). The mixture was stirred at room temperature for 18 hours. The crude mixture was then diluted with ethyl acetate and washed, respectively, with brine, saturated NaHCO3 and brine, and dried over Na2SO4. The organic layer was then concentrated down on rotovap and purified on normal phase column chromatography. Yield=7.27 g (100%). washed respectively, with brine, saturated NaHCO3 and brine, and dried over Na2SO4 The organic layer was then concentrated down on rotovap purified on normal phase column chromatography

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

Procedure: (S)-Benzyl 2-(tert-butoxycarbonylamino)-4-hydroxybutanoate (5.76 g, 18.62 mmol) and 1,3-benzodithiol-2-ylium tetrafluoroborate (4.69 g, 19.55 mmol) were dissolved in dichloromethane (186 mL) and pyridine (4.42 g, 55.86 mmol) was added at room temperature. The mixture was stirred overnight. Upon completion of the reaction, it was quenched with triethylamine (11.5 g, 113.5 mmol) and diluted with dichloromethane. The organic layer was then washed with saturated NaHCO3 and brine. The organic layer was dried over MgSO4 and concentrated down in vacuo. The residue was then purified on normal phase column to obtain a clear oil. 7.6 g (88%). Upon completion of the reaction, it The organic layer was then washed with saturated NaHCO3 and brine The organic layer was dried over MgSO4 concentrated down in vacuo The residue was then purified on normal phase column to obtain a clear oil

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

Procedure: N-t-Boc-L-homoserine (5.14 g, 23.45 mmol) and potassium bicarbonate (2.46 g, 24.6 mmol) was weighed out in a round bottom flask and to it was added anhydrous N,N-dimethylformamide (100 mL) and benzyl bromide (4.2 g, 24.6 mmol). The mixture was stirred at room temperature for 18 hours. The crude mixture was then diluted with ethyl acetate and washed, respectively, with brine, saturated NaHCO3 and brine, and dried over Na2SO4. The organic layer was then concentrated down on rotovap and purified on normal phase column chromatography. Yield=7.27 g (100%). washed respectively, with brine, saturated NaHCO3 and brine, and dried over Na2SO4 The organic layer was then concentrated down on rotovap purified on normal phase column chromatography

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

Procedure: (S)-2-tert-Butoxycarbonylamino-succinic acid 1-benzyl ester (2.62 g, 8.10 mmol) under an atmosphere of nitrogen was dissolved in THF (40 mL) and cooled to 0° C. A 1.0 M borane-THF complex in THF (15 mL) was added dropwise and the reaction mixture was stirred for 3 h, quenched carefully with MeOH (20 mL) and stirred for 20 min. The reaction mixture was treated with MeOH (2×15 mL) and concentrated to dryness. The residue was dissolved in EtOAc and washed with 1N HCl (10 mL), saturated sodium bicarbonate (10 mL), and brine (10 mL). The organic extract was dried over sodium sulfate, filtered and purified on SiO2 to give the intermediate (S)-2-tert-butoxycarbonylamino-4-hydroxy-butyric acid benzyl ester as a clear colorless oil (1.2 g), which was used in the procedure of Preparation 14 to prepare the title compound. quenched carefully with MeOH (20 mL) stirred for 20 min The reaction mixture was treated with MeOH (2×15 mL) concentrated to dryness The residue was dissolved in EtOAc washed with 1N HCl (10 mL), saturated sodium bicarbonate (10 mL), and brine (10 mL) The organic extract was dried over sodium sulfate filtered purified on SiO2

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

Procedure: A solution of di-tert-butylcarbonate (36.40 g, 166.8 mmol) in dioxane (100 ml) was added to a solution of (±)-α-amino-γ-butyrolactone hydrobromide (25.28 g, 138.9 mmol) in a mixture of dioxane/water=1/1 (200 ml). 20 minutes were spent in adding dropwise a solution of sodium hydroxide (12,58 g, 321.1 mmol) in water (100 ml) to the mixture with ice-cooling and with stirring. This mixture was stirred for 30 minutes with ice-cooling and then at room temperature for 3 hours. The reaction mixture was concentrated under reduced pressure. Water (300 ml) was added to the residue and the mixture was acidified by citric acid (25 g) and extracted with ethyl acetate. The organic layer was washed with water, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was dissolved in ethanol (200 ml), and a solution of sodium hydroxide (5.44 g, 138.9 mmol) in water (33 ml) was added to the solution with ice-cooling. After this mixture was allowed to stand at room temperature overnight, it was concentrated under reduced pressure. The resulting residue was dissolved in N,N-dimethylformamide (150 ml), benzyl bromide (16.5 ml, 138.7 mmol) was added to the solution, the mixture was stirred at room temperature overnight, and then it was concentrated under reduced pressure. To the residue, a saturated aqueous solution of ammonium chloride was added and this was extracted with ethyl acetate. The organic layer was washed with water, dried over anhydrous magnesium sulfate and concentrated under reduced pressure to give the title compound (39.75 g, yield 93%) as a pale yellow oil. 20 minutes cooling This mixture was stirred for 30 minutes with ice- cooling The reaction mixture was concentrated under reduced pressure Water (300 ml) was added to the residue extracted with ethyl acetate The organic layer was washed with water dried over anhydrous magnesium sulfate concentrated under reduced pressure The residue was dissolved in ethanol (200 ml) cooling to stand at room temperature overnight it was concentrated under reduced pressure The resulting residue was dissolved in N,N-dimethylformamide (150 ml) the mixture was stirred at room temperature overnight it was concentrated under reduced pressure To the residue, a saturated aqueous solution of ammonium chloride was added this was extracted with ethyl acetate The organic layer was washed with water dried over anhydrous magnesium sulfate concentrated under reduced pressure

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

Procedure: In a similar manner to that described in Example 1(1), a reaction was carried out using (±)-N-(tert-butoxycarbonyl)homoserine benzyl ester, instead of (±)-N-(tert-butoxycarbonyl)homoserine allyl ester, and using 1-benzyloxymethyl-5-fluoro-pyrimidin-2,4-dione instead of phthalimide, to afford the desired compound (yield 54%) as a pale yellow oil.

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

Procedure: In a similar manner to that described in Example 1(1), a reaction was carried out using (±)-N-(tert-butoxycarbonyl)homoserine benzyl ester, instead of (±)-N-(tert-butoxycarbonyl)homoserine allyl ester, and using 1-benzyloxymethyl-5-methyl-pyrimidine-2,4-dione, instead of phthalimide, to afford the desired compound (yield 69%) as a pale yellow oil.

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

Procedure: In a similar manner to that described in Example 1(1), a reaction was carried out using (±)-N-(tert-butoxycarbonyl)homoserine benzyl ester, instead of (±)-N-(tert-butoxycarbonyl)homoserine allyl ester, and using 1-benzyloxymethyl-5-methyl-pyrimidine-2,4-dione, instead of phthalimide, to afford the desired compound (yield 51%) as a white powder.

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

Procedure: In a similar manner to that described in Example 1(1), a reaction was carried out using (±)-N-(tert-butoxycarbonyl)homoserine benzyl ester, instead of (±)-N-(tert-butoxycarbonyl)homoserine allyl ester, and using 1-benzyloxymethylpyrimidine-2,4-dione, instead of phthalimide, to afford the desired compound (yield 74%) as a pale yellow oil.