Solution and Solid Phase Synthesis of Unusual a-Amino Acids From

5.4.1 (2S)-2-[(Be~loxy)carbony1]amin&methoxy~xobutanoic acià, Cbz-L-
Asp-(0Me)-OH, 5.32.
Aspartic acid 5.31 (10.0 g, 0.075 mol) was suspended in freshly distilled MeOH (250
. - mL) and cooled to 0°C whilst stirring under Ar. Chlorotrimethylsilane (1 1.8 rnL, 0.094
mol) was slowly added by dropping funne1 and after 30 min allowed to warm to ambient
temperature. After 2 hours the mixture was cooled to 0°C and a second aliquot of
c hlorotrimethy lsilane (1 1.8 mL, 0.094 mol) slowly added. After 24 hours the solven t was
removed in vucuo, revealing an oil which was placed under high vacuum. De-ionized
water (150 mL) was added to the oil followed by slow addition of Na2C03 (10.23 g,
0.083 mol) to prevent excessive frothing. Once the oil was completely in solution it was
cooled to 0°C and N-(benzyoxycarbony1)-succinimide (18.7 g, 0.075 mol), pre-dissolved
in 1,4-dioxane (150 mL), slowly added to the stimng mixture which was then allowed to
warm to rmm temperature. After 24 hours, the volume was reduced to approximately
200 mL under vacuum, then de-ionized water (100 mL) added and the final pH of the
mixture adjusted to 3 with 1M KI. This was then extracted with CH2C12 (3 x 150 mL),
the organic extracts were then pooled and extracted with saturated NaHC03 (3 x 100
mL). The aqueous extracts were pooled, chilled to 0°C. acidified to pH 3 with IM HCl
then extracted with CH2C12 (4 x 100 mL). The organic extracts were pooled, extracted
with brine (50 mL) then dned over MgS04 and the solvent removed under reduced
pressure to yield a colourless oil which was used without further purification.