Boron trifluoride etherate → 4-(3,4-Dinitrobenzyl)morpholine

Temperature

0 °C

Sodium borohydride (3.36 g, 89 mmol, 2.1 eq.) was ground, placed in a nitrogen-flushed flask and suspended in THF (120 mL). After cooling to ˜0° C., boron trifluoride etherate (11.3 mL, 89 mmol, 2.1 eq.) was added via syringe. This reaction is mildly exothermic and some hydrogen evolution was noted. 4-(3,4-Dinitrobenzoyl)morpholine (11.91 g, 42 mmol, 1.0 eq.) was added as a solid in one portion, the vessel being rinsed with an additional portion of THF (20 mL). The ice-bath was removed and the suspension stirred at r.t. for 3 h before cooling again in ice. Methanol (100 mL) was added cautiously (hydrogen evolution) then the mixture was brought to reflux for 1 h. The mixture was concentrated in vacuo then the residue was partitioned between ethyl acetate (100 mL) and 1:1 saturated sodium bicarbonate solution/water (100 mL). The organic phase was separated, washed with water (50 mL) then brine (100 mL) and dried (MgSO4). The initial bicarbonate wash was extracted a second time with ethyl acetate (50 mL), this extract then being washed with the same aqueous washes used for the first extract before drying (MgSO4), combination and concentration to afford 10.97 g of crude material. Recrystallisation from methanol (45 mL, 10 mL wash) gave the title compound (9.34 g, 83%).

1. customflushed flask
2. washthe vessel being rinsed with an additional portion of THF (20 mL)
3. customThe ice-bath was removed
4. temperaturebefore cooling again in ice
5. additionMethanol (100 mL) was added cautiously (hydrogen evolution)
6. temperatureto reflux for 1 h
7. concentrationThe mixture was concentrated in vacuo
8. customthe residue was partitioned between ethyl acetate (100 mL) and 1:1 saturated sodium bicarbonate solution/water (100 mL)
9. customThe organic phase was separated
10. washwashed with water (50 mL)
11. dry with materialbrine (100 mL) and dried (MgSO4)
12. washThe initial bicarbonate wash
13. extractionwas extracted a second time with ethyl acetate (50 mL)
14. extractionthis extract
15. washthen being washed with the same aqueous washes
16. extractionfirst extract
17. custombefore drying
18. concentration(MgSO4), combination and concentration
19. customto afford 10.97 g of crude material
20. customRecrystallisation from methanol (45 mL, 10 mL wash)

ORD record

ord-8a0de2dae8f1423b9234e2a3c7f8c545

Source dataset

uspto-grants-2013_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08399442B2