Ethyl 4-chloroacetoacetate → Ethyl (3S)-4-chloro-3-hydroxybutanoate

A 600 ml stainless steel Parr reactor was charged with ethanol (340 ml) and ethyl-4-chloroacetoacetate (53 g). The reactor agitator was started and the speed set to 600 rpm. The reactor was pressurised using nitrogen to 7 bar and stirring continued for 5 minutes. After 5 minutes the reactor was slowly vented to ambient pressure, the pressurisation/depressurisation cycle was repeated for a total of five times to ensure complete removal of dissolved oxygen. At the end of the last cycle the reactor set-point temperature was adjusted to 95° C. (R)-[RuCl2(BINAP)]n catalyst was accurately weighed (23 mg) into a catalyst transfer vessel and the vessel then purged using nitrogen for 5 minutes. The catalyst was flushed from the transfer vessel using deoxygenated solvent into a 100 ml stainless steel injection bomb which was attached to the Parr reactor. When the Parr reactor temperature was between 95° C. and 100° C. the injection bomb was pressurised to 100 bar using hydrogen. Appropriate valves were then opened to transfer the catalyst mixture and hydrogen into the reactor. The contents of the reactor were stirred at 600 rpm for 30 minutes before being cooled to less than 30° C. The reactor was then slowly vented to ambient pressure. The reactor contents were transferred into a 1 L rotary film evaporator flask and the mixture evaporated to constant weight by application of vacuum and by using a heated water bath. The residue was subjected to pot to pot distillation under vacuum to afford a clear colourless oily liquid product of ethyl (S)-(−)-4-chloro-3-hydroxybutyrate in >98% yield, >98% purity and 94% enantiomeric excess.

1. waitAfter 5 minutes the reactor was slowly vented to ambient pressure
2. customremoval of dissolved oxygen
3. customwas adjusted to 95° C.
4. customthe vessel then purged
5. customfor 5 minutes
6. customThe catalyst was flushed from the transfer vessel
7. customusing deoxygenated solvent into a 100 ml stainless steel injection bomb which
8. customwas between 95° C. and 100° C.
9. stirringThe contents of the reactor were stirred at 600 rpm for 30 minutes
10. temperaturebefore being cooled to less than 30° C
11. customThe reactor contents were transferred into a 1 L rotary film evaporator flask
12. customthe mixture evaporated to constant weight by application of vacuum
13. distillationpot to pot distillation under vacuum

ORD record

ord-ccb0f26c199d4ad6baa64f94fcbae716

Source dataset

uspto-grants-2006_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07057064B2