Page 133 - Catalysts for Fine Chemical Synthesis Vol 1 - Robert & Poignant

120 hydrolysis, oxidation and reduction

5. The Schlenk tube containing the catalyst was filled with degassed methanol
(20 mL) and methyl acetoacetate (100 mL); the brown suspension was
placed under nitrogen.
6. The Schlenk tube was connected to a low-pressure hydrogenation appar-
atus fitted with a gas burette system to measure the hydrogen consumed.
The Schlenk tube was flushed through three cycles (reduced pressure/
hydrogen) and then placed under an atmospheric pressure of hydrogen.
The burette was filled with 200 mL of hydrogen.
Never allow naked flames in the vicinity when hydrogen is being used.
Avoid the formation of air±hydrogen mixtures. Any electrical appar-
atus in the vicinity must be spark-proof. It is far better for the apparatus
to be kept in a separate room specially designed for hydrogenations.

7. The solution was vigorously stirred to increase the contact area of the
reactants with the hydrogen atmosphere. The solution became lighter
brown. The reaction was stopped after 48 hours (no more hydrogen was
consumed), by removing the hydrogen using reduced pressure.
8. The reaction was monitored by TLC (eluent: petroleum ether±ethyl acet-
ate; 75:25). The methyl acetoacetate was UV active, stained yellow with p-
anisaldehyde, R f 0.5. No starting material remained after 48 hours.
9. The solution was filtered through a pad of silica gel to remove the catalyst
and the filter residue was washed with methanol. The solvent was removed
under reduced pressure using a rotary evaporator (water bath at 30 8C) to
give a slightly brown oil.
10. The residue was distilled with a Kugelrohr apparatus under water aspirator
vacuum (approximately 20 mbar, 140 8C) to give (S)-methyl-(3)-hydroxy-
butanoate (105 mg, 99 %).
The ee (>98 %) was determined by chiral GC (Lipodex 1 E, 25 m,
0.25 mm ID, temperatures: column 90 8C isotherm, injector 250 8C, detector
250 8C, mobile phase helium). R t (R)-enantiomer: 13.5 min; R t (S)-enantio-
mer: 15.2 min.
1 H NMR (200 MHz, CDCl 3 ): d 4.22 (m, 1H, CHOH); 3.72 (s, 3H,
OCH 3 ); 2.56 (br s, 1H, OH); 2.46 (d, J 6.3 Hz, 2H, CH 2 ); 1.23 (d, J 6.1 Hz,
3H, CH 3 CHOH).
‡
Mass: calculated for C 5 H 10 O 3 : m/z 118.06299, found [M] 118.06286.

Conclusion
Hydrogenation with Noyori's catalyst required a customized rig for hydrogen-
ation at high pressure to give good results for a large range of substrates. The
Gene Ãt modification does not require pressure and the catalyst can be prepared
in situ which made the reaction very easy to carry out. Table 9.1 gives examples
of the different substrates which can be hydrogenated by Noyori's [37] and
Gene Ãt's methods [35] .