Potassium Hydroxide → HCID 54549299, compound

At the same time, an elegant asymmetric glycine enolate reaction was developed by Evans and Weber for the synthesis of MeBmt and other chiral amino acids. [See Evans, D. A. and Weber, A. E., J. Am. Chem. Soc. 108:6757 (1986)]. The approach was also applied to prepare MeLeu(OH) [see FIG. 6]. In the reaction sequence, the chiral glycine synthon isothiocyanate was obtained from corresponding chloroacetate and followed by azide replacement in 56% yield. The isothiocyanate chiral auxiliary was condensed with isobutyraldehyde under stannous triflate mediated aldol reaction (-78° C. for 4 h) to give the aldol adduct in 63% yield (>90% e.e). Transesterification with a solution of magnesium methoxide in methanol at room temperature for 3 min gave the methyl ester in 78-82% yield. The yield of the bis-methylation was low, 52% as compared to 76% of Evans in MeBmt synthesis. Two epimers are usually obtained in a ratio of 1:5, which was not found by Evans for the MeBmt synthesis. The 1H NMR spectra of the epimers were compared as shown in Table 4 and FIG. 7. Hydrolysis of the desired trans-oxazolidinone with 2N KOH under reflux gave the pure β-hydroxy-N-methylleucine (see 1H NMR spectra in FIG. 8) after chromatographic purification over Sephadex LH-20.

1. customsynthesis
2. customTwo epimers are usually obtained in a ratio of 1:5, which
3. temperatureunder reflux

ORD record

ord-b9cef91e13fd4da3a68df86b976bdc05

Source dataset

uspto-grants-1997_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05639852