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

2.2.3.2 Ortho Ester Cleavage
Concomitant cleavage of the ortho ester occumd dunng Boc cleavage with
exposure to wet TFA giving the 2-methyl-2-hydroxymethyl-1.3-propanediol ester (mphd)
derivative 2.62.
Several multi-step methods have been reported in the literanire for removing
bicyclic ortho esters (Section 1.4.1). One employs acid hydrolysis to initially open the
ortho ester and base hydrolysis to generate the acid or transesterification of the ring
opened ortho ester to a methyl ester followed by base hydrolysis of the methyl ester to
give the acid with yields normally ~60%.~' Removai of the mphd ester by the methods
described above was found to be unsuccessiÙl.62 However, alkali carbonates have been
show to be more efficient at ester hydrolysis than bicarbonate^^^ and the combination of
Cs2C03 in MeOH:H20 was highiy effective in cleaving the ringspened rnhpd ester 2-62
to the acid 2.53.
Scheme 2.23
The optirnized one-pot procedure consists of concurrent cleavage of the Boc
protecting group and the OB0 ester to the rnhpd ester 2.62 with TFA. Mer evaporation
to dryness, the residue was dissolved in methanol to which a solution of 10% CsK03 was
added in an amount to ensure at least 5 equivalents of base was added.