Reaktion #490336

Reaktionsgleichung

Glucose

2′,6′-dichloro-3′-fluoroacetophenone

hydrochloric acid

NaOH

Magnesium sulfate

→

(S)-1-[2′,6′-dichloro-3′-fluorophenyl]-ethanol

Ausbeute 94.7%

Lösungsmittel

water

Reaktionsbedingungen

Aufarbeitung

1. 1
   workup.ADDITIONa pH electrode connected to an automatic titrator for pH-controlled addition of base on-demand via a delivery tube into the vessel
2. 2
   Temperaturwith heating fluid
3. 3
   Temperaturto maintain the pH at 7.0±0.1
4. 4
   Sonstigethe reaction
5. 5
   WaschenThe electrode required periodic rinsing
6. 6
   Sonstigeto remove enzyme
7. 7
   workup.ADDITIONAdditional glucose was added in portions as the reaction
8. 8
   workup.ADDITION10 g at 104 min (after 17.5 mL of 4 N NaOH had been added), 5 g at 275 min
9. 9
   workup.ADDITION(after 35.2 mL of 4 N NaOH had been added), 5 g at 379 min
10. 10
    workup.ADDITION(after 42 mL of 4 N NaOH had been added), and 8 g at 488 min
11. 11
    workup.ADDITION(after 47 mL of 4 N NaOH had been added)
12. 12
    workup.ADDITIONHeptane (150 mL) was then added
13. 13
    Temperaturthe mixture was heated to 40° C. for 45 min
14. 14
    TemperaturAfter cooling to 30° C. the resulting mixture
15. 15
    workup.ADDITIONwas poured into a separatory funnel
16. 16
    FiltrationThe top layer, a heptane emulsion, was filtered
17. 17
    Filtration(350 mL, 85 mm diameter coarse filter) through a celite pad under vacuum
18. 18
    WaschenThe filter was washed with heptane (150 mL)
19. 19
    Sonstigethe filtrate was transferred to a separatory funnel
20. 20
    Sonstigethe two phases were separated
21. 21
    EinengenThe heptane phase was concentrated on a rotary vacuum evaporator (˜50° C., ˜150 mmHg increasing to 40 mmHg)

Vorschrift

To a 500 mL jacketed three neck round bottom flask equipped with an Ace Glass mechanical stirrer (75 mm diameter teflon stirrer blade), and a pH electrode connected to an automatic titrator for pH-controlled addition of base on-demand via a delivery tube into the vessel, was added water (120 mL), triethanolamine (1.8 g) and then hydrochloric acid to adjust the pH to 7.0. Magnesium sulfate was added as a 1M solution (120 μL, 0.12 mmoles, 14.4 mg of MgSO4). The solution was heated to 30° C. with heating fluid circulating through the flask's jacket. Glucose (20 g) was added followed by Na-NADP (120 mg), GDH (0.50 g) and KRED having SEQ ID No. 38 (0.50 g). The pH stat was set to maintain the pH at 7.0±0.1 by the addition of 4N NaOH through the delivery tube. 2′,6′-dichloro-3′-fluoroacetophenone (50 g) was added to start the reaction. The electrode required periodic rinsing to remove enzyme derived material. Additional glucose was added in portions as the reaction proceeded: 10 g at 104 min (after 17.5 mL of 4 N NaOH had been added), 5 g at 275 min (after 35.2 mL of 4 N NaOH had been added), 5 g at 379 min (after 42 mL of 4 N NaOH had been added), and 8 g at 488 min (after 47 mL of 4 N NaOH had been added). The reaction was stopped after 24 hr. Heptane (150 mL) was then added and the mixture was heated to 40° C. for 45 min. After cooling to 30° C. the resulting mixture was poured into a separatory funnel and the majority of the bottom aqueous layer was drained. The top layer, a heptane emulsion, was filtered (350 mL, 85 mm diameter coarse filter) through a celite pad under vacuum. The filter was washed with heptane (150 mL) and the filtrate was transferred to a separatory funnel and the two phases were separated. The heptane phase was concentrated on a rotary vacuum evaporator (˜50° C., ˜150 mmHg increasing to 40 mmHg) to yield (S)-1-[2′,6′-dichloro-3′-fluorophenyl]-ethanol as an oil (47.8 g, 94%) which crystallized upon standing.

Quelle