Improved Methodology for the Preparation of Chiral Amines

stopping the hydrogenation, further MeOH was added, and this heterogeneous solution was
filtered to remove the Raney-Ni, and excess ethereal HCl was added. This was concentrated
to dryness (rotary evaporation) and then aqueous HCl (2.0 M) and ether were added. The
acidic aqueous layer was removed and the Et 2 O was extracted with further extracted with
aqueous HCl (2.0 M, 2 × 15 mL). The aqueous acidic layer was basified with NaOH (4.0 M)
to a pH= 12-14 and the free amine extracted with CH 2 Cl 2 (4 x 20 mL). The combined organic
extracts were dried over Na 2 SO 4 , filtered and to the filtrate ethereal HCl (2.0 M, 4.0 mL) was
added. This solution was concentrated on rotary evaporator and after high vacuum drying
(≥24 h) afforded the HCl salt (0.42 g, 79% yield) after high vacuum drying. GC (program B,
see Experimental section (general remarks)): retention time [min] for the free base: major
(S,S)-2f isomer, 13.0; minor (R,S)-2f isomer, 12.7. The NMR data of (S,S)-2f (free base)
matches that reported in the literature. [2]
Major (S,S)-2f: 1 H NMR (CDCl3, 400 MHz,): δ 7.38-7.20 (m, 5H), 3.87 (q, J = 6.4 Hz, 1H),
2.49-2.41 (m, 1H), 1.56-1.49 (m, 1H), 1.34-1.24 (m, 5 H), 0.95 (d, J = 6.4 Hz, 3H), 0.84 (t, J
= 7.2 Hz, 3H). 13 C NMR (CDCl3, 100 MHz): δ 146.4, 128.3, 126.7, 126.5, 55.0, 51.3, 28.6,
24.7, 20.7, 9.8.
(2S)-3,3-Dimethyl-N-((S)-1-phenylethyl)butan-2-amine (2b) (Pt substrate)
In a reaction vessel dry Yb(OAc) 3 (0.96 g, 2.75 mmol, 1.1 equiv) was added and
subsequently evacuated under high vacuum for 5 min before flooding with nitrogen,,
anhydrous MeOH (2.5 mL, 1.0 M) was then added. To this solution 3,3-Dimethyl-2-butanone
(0.31 mL, 2.5mmol, 1.0 equiv), (S)-α-methylbenzylamine (0.35 mL, 2.75 mmol, 1.1 equiv)
were added. The reaction was then stirred at 50 ºC for 2 h. Pt-C (98.0 mg, 1.0 mol %) [The 98
mg of Pt/C was added in four equal portions, thus 24.5 mg at t= 0 h, t= 2 h, t= 4 h, and finally
at t= 6 h] and THF (2.5 mL, final molarity of reaction vessel 0.5 M) was then added and the
reaction vessel pressurized at 120 psi (8.3 bar) of hydrogen. The reaction was then stirred at
50 ºC. After 22 h (