Page 145 - Catalysts for Fine Chemical Synthesis Vol 1 - Robert & Poignant

132 hydrolysis, oxidation and reduction

Procedure

1. A solution of ethyl (1S,3R,4R)-2-[(S)-1-phenylethylamino]-2-azabicyclo
[2.2.1]hept-5-ene-3-carboxylate (major exo-Diels±Alder adduct) (10 g,
36.9 mmol) in absolute ethanol (60 mL) was stirred under a hydrogen pressure
of 150 psi at room temperature for 48 hours in the presence of activated 5 %
Pd±C (2 g, 20 wt%).
2. The Pd±C catalyst was then removed by filtration through Celite in a
sintered glass funnel with the aid of a water aspirator. The filtration was
completed by rinsing the packing with 95 % ethanol (75 mL). Attention: due
to the pyrophoric properties of hydrogen-saturated palladium, it is important
to keep the filter plug under a layer of ethanol.
3. The filtrate was transfered to a 250 mL round bottomed flask and the
solvent was removed using a rotary evaporator to afford the corresponding
pure amino ester as a pale yellowish oil (6.11 g, 98 % yield).
The ee (98 %) of the ligand was determined at this point as its N-benzoyl
derivative [44] by HPLC (ChiralCelOD-H, 254 nm UV detector, flow 0.4 mL/
min, eluent hexane/i-PrOH: 80/20); R t (minor) 15.0 min, R t (major) 22.9 min.
1
H NMR (400 MHz, CDCl 3 ): d 1.21 (1 H, br d, J 9.8 Hz), 1.25 (3 H, t, J
7.1 Hz), 1.34±1.66 (5 H, m), 2.18 (1 H, br s), 2.59, 3.27, 3.50 (1 H each, 3 br s)
and 4.15 (2 H, q, J 7.1 Hz).
4. Lithium aluminium hydride (8.4 g, 215 mmol) was placed in a 250 mL round
bottomed flask equipped with a magnetic stirrer bar and flushed with
nitrogen. Dry tetrahydrofuran (120 mL) was added and the suspension
was cooled with the aid of an ice-bath.
5. A solution of the amino ester (6.11 g, 36.2 mmol) in dry tetrahydrofuran
(10 mL) was carefully, dropwise added to this supension. When the addition
was complete, the mixture was stirred for 30 minutes at room temperature.
6. After completion according to TLC, the reaction was quenched adding
consecutively 8.4 mL of water, 8.4 mL of 15 % NaOH solution and
25.2 mL of water. The mixture was then stirred for 30 min at room tempera-
ture.
7. The aluminates were removed by filtration through a sintered glass funnel
with the aid of the water aspirator. The filtration was completed by rinsing
the packing with tetrahydrofuran (75 mL).
8. Solvent evaporation in a rotary evaporator afforded the amino alcohol
product (4.14 g, 90 % yield). The purity of the crude product is high enough
to be used in the catalysis experiments, but it can be purified further by
vacuum distillation in a Kugelrohr [90±100 8C, 0.030±0.035 mbar] cooling
the recipient flask with dry ice (84 % yield from the amino ester, as white
needles).
1
H NMR (400 MHz, CDCl 3 ): d 1.15 (1 H, dt, J 9.8, 1.4 Hz), 1.40±1.30 (2
H, m), 1.72±1.53 (3 H, m), 2.17 (1 H, m), 2.89±2.79 (3 H, m), 3.17 (1 H, dd, J
10.7, 8.2 Hz), 3.40 (1 H, dd, J 10.7, 5.4 Hz) and 3.43 (1 H, br s).