B. Li et al. / Tetrahedron Letters 44 (2003) 8113–8115
8115
19. For reactions of milligram scales, 0.5 mL of the solvent
and 0.5 mL of aqueous 85% H3PO4 were used.
References
20. It is possible to heat the reaction to accelerate the reac-
tion to reduce the amount of reagent used when no other
acid sensitive functionalities are present. Methyl and ben-
zyl esters, and the isopropylidene group were partially
deprotected at 50°C under the reaction conditions.
21. Typical procedure for BOC deprotection: To a solution
of 2-tert-butoxycarbonylamino-succinic acid 1-benzyl
ester (1.0 g, 2.73 mmol) in tetrahydrofuran (1 mL) at
room temperature (entry 1, Table 1), was added aqueous
phosphoric acid (85 wt%, purchased from Aldrich Chem-
ical Co.) (2.81 mL, 41 mmol) dropwise. The mixture was
stirred for 4 h, and HPLC assay showed reaction comple-
tion. 5 mL of water was added, and the mixture was
cooled to 0°C. 50 wt% NaOH solution was added slowly
(Caution: exothermic) to adjust to the pH to ꢀ8. The
mixture was then extracted with ethyl acetate (2×20 mL).
The combined ethyl acetate phase was dried over magne-
sium sulfate, concentrated in vacuo to give the desired
product as a white solid (0.57 g, 94%). The product
showed 98.7% HPLC purity (by area%). It co-eluted with
an authentic sample by HPLC.
22. Isolated yields. All products were characterized by NMR
and MS. Achiral HPLC analyses were carried out in
HP-1100 (Model) using a stable-bond cyano (SB-CN)
column (4.6 mm×250 mm) with acetonitrile: 0.2%
perchloric acid aqueous buffer (20/80 or 40/60) as mobile
phase (2 mL/min) and detection at 210 nm wavelength.
Chiral HPLC methods were used for the assays: Chiral-
Pak AD-H column, 4.6×250 mm, hexane:ethanol:diethyl-
amine (90/10/0.2) mobile phase, 1.5 mL/min. 35°C, 210
or 225 nm.
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