Reaktion #2155693

Reaktionsgleichung

HCl

7,9-dimethyl-3,4-dihydro-1H-benzo[b]azepin-5(2H)-one hydrochloride

2-methyltetrahydrofuran

water

Na2CO3

benzyl chloroformate

→

title compound

Ausbeute 91.9%

Benzyl 7,9-dimethyl-5-oxo-2,3,4,5-tetrahydro-1H-benzo[b]azepine-1-carboxylate

Ausbeute 91.9%

Reaktionsbedingungen

Aufarbeitung

1. 1
   workup.ADDITIONCharge a 22 L flask with an overhead stirrer
2. 2
   workup.ADDITIONthermocouple, 3 L addition funnel
3. 3
   Temperaturbaffle, cooling bath
4. 4
   SonstigeN2 purge
5. 5
   workup.ADDITIONCharge
6. 6
   workup.ADDITIONadd dropwise to the reaction
7. 7
   Temperaturwhile maintaining the reaction mixture below about 15° C
8. 8
   Sonstigeequipped with a condenser
9. 9
   Temperaturheat to 25-25° C.
10. 10
    TemperaturCool to about 15° C.
11. 11
    SonstigeSeparate the layers
12. 12
    ExtraktionExtract the aqueous layer with methyltetrahydrofuran (4 L)
13. 13
    Waschenwash with water (4 l)
14. 14
    EinengenConcentrate the organic layer at about 40° C
15. 15
    EinengenAdd IPA (4 L) and then concentrate to 2 L
16. 16
    SonstigeTransfer to a 12 L flask equipped with an overhead stirrer
17. 17
    Temperaturthermocouple, heating mantle
18. 18
    workup.ADDITIONcondenser, 2 L addition funnel
19. 19
    SonstigeN2 purge
20. 20
    TemperaturHeat the flask contents to about 70-80° C.
21. 21
    workup.ADDITIONadd heptane (5 L)
22. 22
    TemperaturSlowly cool to RT overnight
23. 23
    Sonstigecrystallization of the titled compound
24. 24
    TemperaturCool
25. 25
    Sonstigecollect the solid
26. 26
    Waschenrinse the solid with cold heptane
27. 27
    Sonstigedry in a vacuum at 50° C.

Vorschrift

Charge a 22 L flask with an overhead stirrer, thermocouple, 3 L addition funnel, baffle, cooling bath and N2 purge and 7,9-dimethyl-3,4-dihydro-1H-benzo[b]azepin-5(2H)-one hydrochloride (1,000 g, 4.43 moles). Add 2-methyltetrahydrofuran (6.44 kg, 7.5 L, 74.5 moles) and agitate the off-white slurry. Cool to 5-15° C. Add water 2.5 L, 138.8 moles and Na2CO3 (1.12 kg, 3 moles) to the addition funnel then slowly add to the reaction mixture at a fast drip over about 25 m. Charge a 2 L addition funnel with benzyl chloroformate (91.59 kg, 8.86 moles) add dropwise to the reaction, while maintaining the reaction mixture below about 15° C. Transfer the resulting mixture to a flask equipped with a condenser and heat to 25-25° C. and stir for about 50 h. Cool to about 15° C., add HCl (5 M, until the pH is about 5). Separate the layers. Extract the aqueous layer with methyltetrahydrofuran (4 L); combine the organic layers and wash with water (4 l). Concentrate the organic layer at about 40° C. Add IPA (4 L) and then concentrate to 2 L. Transfer to a 12 L flask equipped with an overhead stirrer, thermocouple, heating mantle condenser, 2 L addition funnel and N2 purge. Heat the flask contents to about 70-80° C. and add heptane (5 L). Slowly cool to RT overnight; seed the mixture if necessary to induce crystallization of the titled compound. Cool and collect the solid; rinse the solid with cold heptane and dry in a vacuum at 50° C. to provide 1,316 g of the title compound.

Quelle