M. K. J. ter Wiel et al. / Tetrahedron: Asymmetry 20 (2009) 478–482
481
4.3. (S)-3-Benzyloxycarbonylamino-4,4-dimethylpentanoic
acid,
-(ꢀ)-Norephedrine salt
(160 ml) and water (40 ml) and filled into an autoclave. Palladium
on carbon (1.0 g, 5%) was added, and the mixture was flushed three
times with hydrogen. The reaction mixture was left to stir at 50 °C
for 24 h under 10 bar hydrogen. The catalyst was removed by fil-
tration, leaving a colourless solution. Removal of all volatiles left
the enantiomerically pure amino acid as a white solid (9.77 g,
67.4 mmol, 94.1%); The shifts in the 1H and 13C NMR spectra were
L
Racemic Cbz-protected b-neopentylglycine (150 g, 537 mmol)
was suspended in toluene (1.5 l). This mixture was heated to 80–
90 °C and
L-(ꢀ)-norephedrine (44.7 g, 296 mmol, 0.55 equiv) was
added to the slightly turbid solution as a solid. The resulting solu-
tion was allowed to reach room temperature in 4 h and was then
cooled in an ice bath for 1 h. The solids were filtered off, washed
with cold toluene (2 ꢁ 100 ml) and dried at 50 °C under reduced
pressure. It should be noted that complete removal of all the tolu-
ene can take up to 2 days. The dried solid was weighed (95.3 g,
221 mmol, 41.2%) and analysed by HPLC (ratio (R):(S) = 2.8:97.2).
In order to obtain a diastereomerically pure product, the product
was recrystallised from a mixture of toluene (720 ml) and ethanol
(190 ml). The salt dissolved at close to 100 °C in the solvent mix-
ture and was heated at reflux for 20 min. On cooling to room tem-
perature over ca. 3 h, a fluffy solid formed. After further cooling in
an ice bath and stirring for an additional hour, the solids were iso-
lated by filtration and then dried at 50 °C to give the diastereomer-
ically pure product as a fluffy solid (83.9 g, 194 mmol, 36.1%); 1H
NMR (500 MHz, DMSO-d6) d: 0.83 (s, 9H, t-Bu, b-AA), 0.86 (d,
identical to those reported for the racemate above; ½a D20
¼ ꢀ67:7 (c
ꢂ
1, H2O). The determination of the enantiomeric purity was per-
formed by GC using a Chirasil Dex CB column. Sample preparation:
2.5 mg of the sample was treated with 500 ll 3 M hydrochloric
acid in ethanol (prepared by mixing 37 ml of ethanol and 10 ml
of acetyl chloride) for 45 min at 110 °C. All solvents were removed
in a nitrogen stream and the residue was subsequently treated
with a mixture of 200
tic acid anhydride for 10 min at 110 °C. After removal of all vola-
tiles, the remaining material was dissolved in 150 l of toluene
ll dichloromethane and 200 ll trifluoroace-
l
and analysed. Temperature program: 70 °C for 1 min then an in-
crease of 3 °C minꢀ1 until 160 °C; then at 160 °C for 1 min; sample
volume 0.2 ll; hydrogen gas as mobile phase; split 70:1; The enan-
tiomeric purity of the sample proved to be 99.9% for the (S)-enan-
tiomer; IR (KBr), kꢀ1 (cmꢀ1): 2966, 1639, 1494, 1464, 1387, 1146.
J = 6.5 Hz, 3H, Me,
L
-nor.), 2.13 (dd, J = 15.0, 9.6 Hz, 1H, H2, b-AA),
0
2.34 (dd, J = 15.0, 3.5 Hz, 1H, H2 , b-AA), 3.02–3.12 (m, 1H, H2,
nor.), 3.68–3.82 (m, 1H, H3, b-AA), 4.56 (d, J = 4.2 Hz, 1H, H1,
L
-
-
References
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nor.), 4.95 (d, J = 12.7 Hz, 1 H, Hbenzyl, b-AA), 5.02 (d, J = 12.7 Hz,
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