(2S)-2,3-dihydroxy-N-methoxy-N,2-dimethylpropanamide

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

Procedure: (S)-2,3-dihydroxy-N-methoxy-N,2-dimethylpropanamide (32 g, 196 mmol) was dissolved in 2,2-dimethoxypropane (241 ml, 1961 mmol, 4-methylbenzenesulfonic acid hydrate (3.73 g, 19.6 mmol) was added, and the reaction was stirred at ambient temperature overnight. The reaction was partitioned between CH2Cl2 and saturated aqueous sodium bicarbonate, extracted with CH2Cl2, dried over sodium sulfate, filtered and concentrated. The residue was purified on silica plug (1.5 L, eluting with 25% EtOAc in hexanes) to afford (S)-N-methoxy-N,2,2,4-tetramethyl-1,3-dioxolane-4-carboxamide (23.1 g, 114 mmol, 58.0% yield). was added The reaction was partitioned between CH2Cl2 and saturated aqueous sodium bicarbonate extracted with CH2Cl2 dried over sodium sulfate filtered concentrated The residue was purified on silica plug (1.5 L, eluting with 25% EtOAc in hexanes)

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

Procedure: A round bottom flask was charged with 3BuOH (850 mL), water (850 mL), Ad-Mix-β (230 g, 166 mmol) and methanesulfonamide (15.8 g, 166 mmol). The mixture was stirred at ambient temperature until both phases were clear (about 5 minutes) and then cooled to 0° C., after which orange salts precipitated. N-methoxy-N-methylmethacrylamide (21.5 g, 166 mmol) was added and the heterogeneous slurry was stirred vigorously 0° C. for 2 hours and warmed to ambient temperature and stirred for 24 hours. The reaction was quenched by the slow, portionwise addition of sodium bisufite (223 g) and stirred for 1 hour. The reaction mixture was extracted with EtOAc (3×300 mL), dried over sodium sulfate, filtered and concentrated to afford (S)-2,3-dihydroxy-N-methoxy-N,2-dimethylpropanamide (32 g, 196 mmol, 118% yield) as a yellow oil. (about 5 minutes) cooled to 0° C. after which orange salts precipitated the heterogeneous slurry was stirred vigorously 0° C. for 2 hours warmed to ambient temperature stirred for 24 hours The reaction was quenched by the slow, portionwise addition of sodium bisufite (223 g) stirred for 1 hour The reaction mixture was extracted with EtOAc (3×300 mL) dried over sodium sulfate filtered concentrated

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

Procedure: A round bottom flask was charged with 3BuOH (850 mL), water (850 mL), Ad-Mix-β (230 g, 166 mmol) and methanesulfonamide (15.8 g, 166 mmol). The mixture was stirred at ambient temperature until both phases were clear (about 5 minutes) and then cooled to 0° C., after which orange salts precipitated. N-methoxy-N-methylmethacrylamide (21.5 g, 166 mmol) was added and the heterogeneous slurry was stirred vigorously 0° C. for 2 hours and warmed to ambient temperature and stirred for 24 hours. The reaction was quenched by the slow, portionwise addition of sodium bisufite (223 g) and stirred for 1 hour. The reaction mixture was extracted with EtOAc (3×300 mL), dried over sodium sulfate, filtered and concentrated to afford (S)-2,3-dihydroxy-N-methoxy-N,2-dimethylpropanamide (32 g, 196 mmol, 118% yield) as a yellow oil. (about 5 minutes) cooled to 0° C. after which orange salts precipitated the heterogeneous slurry was stirred vigorously 0° C. for 2 hours warmed to ambient temperature stirred for 24 hours The reaction was quenched by the slow, portionwise addition of sodium bisufite (223 g) stirred for 1 hour The reaction mixture was extracted with EtOAc (3×300 mL) dried over sodium sulfate filtered concentrated

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

Procedure: The compound prepared in Example 130(a) (12.4 g), acetone (150 mL), acetone dimethylacetal (18 mL) and p-toluenesulfonic acid monohydrate (290 mg) were stirred at room temperature for an hour. The reaction mixture was concentrated, poured into a cold aqueous solution of sodium hydrogen carbonate and extracted with a mixed solution of ethyl acetate-hexane (1:1). The obtained organic layer was washed with an aqueous saturated sodium hydrogen carbonate solution, water and brine, and dried over anhydrous magnesium sulfate. The solvent was concentrated in vacuum condition and dried to give the title compound (8.4 g) having the following physical data. The reaction mixture was concentrated poured into a cold aqueous solution of sodium hydrogen carbonate extracted with a mixed solution of ethyl acetate-hexane (1:1) The obtained organic layer was washed with an aqueous saturated sodium hydrogen carbonate solution, water and brine dried over anhydrous magnesium sulfate The solvent was concentrated in vacuum condition dried

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

Procedure: To a solution of the compound prepared in Example 130(a) (565 mg) in methanol (7.0 mL) was added lithium hydroxide monohydrate (146 mg) and the mixture was stirred at room temperature for 4 hours. The reaction mixture was concentrated to give the title compound (446 mg) having the following physical data. The reaction mixture was concentrated

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

Procedure: (S)-2,3-dihydroxy-N-methoxy-N,2-dimethylpropanamide (32 g, 196 mmol) was dissolved in 2,2-dimethoxypropane (241 ml, 1961 mmol, 4-methylbenzenesulfonic acid hydrate (3.73 g, 19.6 mmol) was added, and the reaction was stirred at ambient temperature overnight. The reaction was partitioned between CH2Cl2 and saturated aqueous sodium bicarbonate, extracted with CH2Cl2, dried over sodium sulfate, filtered and concentrated. The residue was purified on silica plug (1.5 L, eluting with 25% EtOAc in hexanes) to afford (S)—N-methoxy-N,2,2,4-tetramethyl-1,3-dioxolane-4-carboxamide (23.1 g, 114 mmol, 58.0% yield). was added The reaction was partitioned between CH2Cl2 and saturated aqueous sodium bicarbonate extracted with CH2Cl2 dried over sodium sulfate filtered concentrated The residue was purified on silica plug (1.5 L, eluting with 25% EtOAc in hexanes)

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

Procedure: A round bottom flask was charged with tBuOH (850 mL), water (850 mL), Ad-Mix-β (230 g, 166 mmol) and methanesulfonamide (15.8 g, 166 mmol). The mixture was stirred at ambient temperature until both phases were clear (about 5 minutes) and then cooled to 0° C., after which orange salts precipitated. N-methoxy-N-methylmethacrylamide (21.5 g, 166 mmol) was added and the heterogeneous slurry was stirred vigorously at 0° C. for 2 hours and warmed to ambient temperature and stirred for 24 hours. The reaction was quenched by the slow, portionwise addition of sodium bisulfite (223 g) and stirred for 1 hour. The reaction mixture was extracted with EtOAc (3×300 mL), dried over sodium sulfate, filtered and concentrated to afford (S)-2,3-dihydroxy-N-methoxy-N,2-dimethylpropanamide (32 g, 196 mmol, 118% yield) as a yellow oil. (about 5 minutes) cooled to 0° C. after which orange salts precipitated the heterogeneous slurry was stirred vigorously at 0° C. for 2 hours warmed to ambient temperature stirred for 24 hours The reaction was quenched by the slow, portionwise addition of sodium bisulfite (223 g) stirred for 1 hour The reaction mixture was extracted with EtOAc (3×300 mL) dried over sodium sulfate filtered concentrated

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

Procedure: (S)-2,3-dihydroxy-N-methoxy-N,2-dimethylpropanamide (32 g, 196 mmol) was dissolved in 2,2-dimethoxypropane (241 ml, 1961 mmol, 4-methylbenzenesulfonic acid hydrate (3.73 g, 19.6 mmol) was added, and the reaction was stirred at ambient temperature overnight. The reaction was partitioned between CH2Cl2 and saturated aqueous sodium bicarbonate, extracted with CH2Cl2, dried over sodium sulfate, filtered and concentrated. The residue was purified on silica plug (1.5 L, eluting with 25% EtOAc in hexanes) to afford (S)-N-methoxy-N,2,2,4-tetramethyl-1,3-dioxolane-4-carboxamide (23.1 g, 114 mmol, 58.0% yield). was added The reaction was partitioned between CH2Cl2 and saturated aqueous sodium bicarbonate extracted with CH2Cl2 dried over sodium sulfate filtered concentrated The residue was purified on silica plug (1.5 L, eluting with 25% EtOAc in hexanes)

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

Procedure: A round bottom flask was charged with 3BuOH (850 mL), water (850 mL), Ad-Mix-β (230 g, 166 mmol) and methanesulfonamide (15.8 g, 166 mmol). The mixture was stirred at ambient temperature until both phases were clear (about 5 minutes) and then cooled to 0° C., after which orange salts precipitated. N-methoxy-N-methylmethacrylamide (21.5 g, 166 mmol) was added and the heterogeneous slurry was stirred vigorously at 0° C. for 2 hours and warmed to ambient temperature and stirred for 24 hours. The reaction was quenched by the slow, portionwise addition of sodium bisulfite (223 g) and stirred for 1 hour. The reaction mixture was extracted with EtOAc (3×300 mL), dried over sodium sulfate, filtered and concentrated to afford (S)-2,3-dihydroxy-N-methoxy-N,2-dimethylpropanamide (32 g, 196 mmol, 118% yield) as a yellow oil. (about 5 minutes) cooled to 0° C. after which orange salts precipitated the heterogeneous slurry was stirred vigorously at 0° C. for 2 hours warmed to ambient temperature stirred for 24 hours The reaction was quenched by the slow, portionwise addition of sodium bisulfite (223 g) stirred for 1 hour The reaction mixture was extracted with EtOAc (3×300 mL) dried over sodium sulfate filtered concentrated

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

Procedure: (S)-2,3-dihydroxy-N-methoxy-N,2-dimethylpropanamide (32 g, 196 mmol) was dissolved in 2,2-dimethoxypropane (241 ml, 1961 mmol, 4-methylbenzenesulfonic acid hydrate (3.73 g, 19.6 mmol) was added, and the reaction was stirred at ambient temperature overnight. The reaction was partitioned between CH2Cl2 and saturated aqueous sodium bicarbonate, extracted with CH2Cl2, dried over sodium sulfate, filtered and concentrated. The residue was purified on silica plug (1.5 L, eluting with 25% EtOAc in hexanes) to afford (S)-N-methoxy-N,2,2,4-tetramethyl-1,3-dioxolane-4-carboxamide (23.1 g, 114 mmol, 58.0% yield). was added The reaction was partitioned between CH2Cl2 and saturated aqueous sodium bicarbonate extracted with CH2Cl2 dried over sodium sulfate filtered concentrated The residue was purified on silica plug (1.5 L, eluting with 25% EtOAc in hexanes)

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

Procedure: A round bottom flask was charged with 3BuOH (850 mL), water (850 mL), Ad-Mix-β (230 g, 166 mmol) and methanesulfonamide (15.8 g, 166 mmol). The mixture was stirred at ambient temperature until both phases were clear (about 5 minutes) and then cooled to 0° C., after which orange salts precipitated. N-methoxy-N-methylmethacrylamide (21.5 g, 166 mmol) was added and the heterogeneous slurry was stirred vigorously 0° C. for 2 hours and warmed to ambient temperature and stirred for 24 hours. The reaction was quenched by the slow, portionwise addition of sodium bisufite (223 g) and stirred for 1 hour. The reaction mixture was extracted with EtOAc (3×300 mL), dried over sodium sulfate, filtered and concentrated to afford (S)-2,3-dihydroxy-N-methoxy-N,2-dimethylpropanamide (32 g, 196 mmol, 118% yield) as a yellow oil. (about 5 minutes) cooled to 0° C. after which orange salts precipitated the heterogeneous slurry was stirred vigorously 0° C. for 2 hours warmed to ambient temperature stirred for 24 hours The reaction was quenched by the slow, portionwise addition of sodium bisufite (223 g) stirred for 1 hour The reaction mixture was extracted with EtOAc (3×300 mL) dried over sodium sulfate filtered concentrated