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

HRID 1622429Notes

Reaction equation

HRID 1622429 reaction equation
[N+:1]([C:4]1[CH:5]=[C:6]([C:13]([N:15]2[CH2:20][CH2:19][O:18][CH2:17][CH2:16]2)=O)[CH:7]=[CH:8][C:9]=1[N+:10]([O-:12])=[O:11])([O-:3])=[O:2].O1CCCC1.B(F)(F)F.CCOCC.[BH4-].[Na+]>CCOCC.CO>[N+:1]([C:4]1[CH:5]=[C:6]([CH:7]=[CH:8][C:9]=1[N+:10]([O-:12])=[O:11])[CH2:13][N:15]1[CH2:20][CH2:19][O:18][CH2:17][CH2:16]1)([O-:3])=[O:2]

Participants

7

Reactant 4

HCID 8000Boron trifluoride etherateHCID 8028TetrahydrofuranHCID 4311764Sodium borohydrideHCID 13043973(3,4-Dinitrophenyl)(morpholino)methanone

Product 1

HCID 251933104-(3,4-Dinitrobenzyl)morpholineYield 98.4%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 3283Diethyl EtherSolvent

Conditions

Temperature
2.5 °C

Procedure

(3,4-Dinitrophenyl)-morpholin-4-yl-methanone (0.750 Kg, 2.67 mol, 1.O wt) and tetrahydrofuran (7.50 L, 1O.O vol) were charged to a flask under nitrogen and cooled to 0 to 5° C. Borontrifluoride etherate (0.713 L, 5.63 mol, 0.95 vol) was added at 0 to 5° C. and the suspension was stirred at this temperature for 15 to 30 minutes. Sodium borohydride (0.212 Kg, 5.60 mol, 0.282 wt) was added in 6 equal portions over 90 to 120 minutes. (A delayed exotherm was noted 10 to 15 minutes after addition of the first portion. Once this had started and the reaction mixture had been re-cooled, further portions were added at 10 to 15 minute intervals, allowing the reaction to cool between additions). The reaction mixture was stirred at 0 to 5° C. for 30 minutes. Reaction completion was determined by 1H NMR analysis (d6-DMSO). Methanol (6.30 L, 8.4 vol) was added dropwise at 0 to 10° C. to quench the reaction mixture (rapid gas evolution, some foaming). The quenched reaction mixture was stirred at 0 to 10° C. for 25 to 35 minutes then warmed to and stirred at 20 to 3O° C. (exotherm, gas/ether evolution on dissolution of solid) until gas evolution had slowed. The mixture was heated to and stirred at 65 to 7O° C. for 1 hour. The mixture was cooled to 30 to 4O° C. and concentrated under vacuum at 40 to 45° C. to give crude 4-(3,4-dinitro-benzyl)-morpholine (0.702 Kg, 98.4%) as a yellow/orange solid.

Workup

  1. wait(A delayed exotherm was noted 10 to 15 minutes
  2. additionafter addition of the first portion
  3. temperaturethe reaction mixture had been re-cooled
  4. additionfurther portions were added at 10 to 15 minute intervals
  5. customthe reaction
  6. temperatureto cool between additions)
  7. stirringThe reaction mixture was stirred at 0 to 5° C. for 30 minutes
  8. customReaction completion
  9. customto quench the reaction mixture (rapid gas evolution
  10. customThe quenched reaction mixture
  11. stirringwas stirred at 0 to 10° C. for 25 to 35 minutes
  12. temperaturethen warmed to and
  13. stirringstirred at 20 to 3O° C
  14. temperatureThe mixture was heated to and
  15. stirringstirred at 65 to 7O° C
  16. waitfor 1 hour
  17. temperatureThe mixture was cooled to 30 to 4O° C
  18. concentrationand concentrated under vacuum at 40 to 45° C.

Sources & evidence

ORD record
ord-eceb8a56f02045f399c82b47220e3c00
Source dataset
uspto-grants-2014_07
Patent number
US08778936B2

Reaction notes

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