Chlorotrimethylsilane → (S)-2-Amino-6,6-dimethoxyhexanoic acid, methyl ester hydrochloride salt

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Reaction Conditions

Reaction Steps

Under nitrogen, (S)-α-amino-1,3-dioxolane-2-pentanoic acid (25.0 g), methanol (300 ml) and dimethyl sulfite (12.32 ml) were added to a 500 ml three-neck round bottom flask equipped with a mechanical stirrer, thermocouple, heater, nitrogen inlet and bubbler. Chlorotrimethylsilane (41.95 ml) was added to the resulting slurry which was heated at 40° C. for 8 hours to give (S)-2-amino-6,6-dimethoxyhexanoic acid, methyl ester, hydrochloride salt. After cooling to about 25° C., the hydrochloride salt solution was neutralized by addition to a slurry of potassium bicarbonate (52.15 g) in methanol (100 ml) at a rate which maintained the pH above 7 (total addition time about 1 hour). n-Butyl acetate (200 ml) was added and the slurry was concentrated under vacuum (110 to 30 torr) keeping the temperature below 30° C. to remove methanol. The neutralized slurry of (S)-2-amino-6,6-dimethoxyhexanoic acid, methyl ester was held at 0-5° C. while the following step was performed.

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