Hydrochloric Acid → HCID 21947523, compound

HRID 2214641Notes

Reaction equation

HRID 2214641 reaction equation
[F:1][C:2]1[CH:18]=[CH:17][C:5]([C:6]([NH:8][CH2:9][C:10]2[CH:15]=[CH:14][C:13]([F:16])=[CH:12][CH:11]=2)=O)=[CH:4][CH:3]=1.B(F)(F)F.CCOCC.S(C)C.[OH-].[Na+].[ClH:33]>C1COCC1.CCOCC>[ClH:33].[F:1][C:2]1[CH:3]=[CH:4][C:5]([CH2:6][NH:8][CH2:9][C:10]2[CH:15]=[CH:14][C:13]([F:16])=[CH:12][CH:11]=2)=[CH:17][CH:18]=1

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 1068Dimethyl SulfideHCID 8000Boron trifluoride etherateHCID 14798Sodium HydroxideHCID 2303704HCID 2303704, compound

Product 1

HCID 21947523HCID 21947523, compoundYield 93%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolvent2×HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-30 °C

Procedure

4-Fluoro-N-(4-fluoro-benzyl)-benzamide (40.0 grams, 0.16 mole) was dissolved in 240 mL of THF. To this was added BF3.Et2O (7.4 mL. 0.06 mole) and the resulting mixture heated to reflux for 15 min. After cooling to −30° C., BH3.SMe2 (22.3 mL, 0.24 mole) was added using a dropping funnel. The reaction was allowed to warm to room temperature. The reaction flask was fitted with a distillation condenser and solvent removed under reflux for 25 min. The distillation apparatus was replaced with a reflux condenser and the reaction heated to 110° C. for 2 h. After cooling to 0° C., 100 mL of 6N HCl was added and the mixture heated to reflux for 1 hr to yield a thick slurry. 300 mL of 6N NaOH was slowly added at room temperature with intermittent cooling using an ice bath. After all the solid has dissolved Et2O was added and the mixture transferred to a separatory funnel. The organic layer was separated, dried over Na2SO4, filtered and the solvent removed under vacuum to yield an oil. The oil was dissolved in 50 mL of Et2O and 4N HCl (dioxane) added resulting in the formation of a white precipitate which was isolated by filtration to yield 40 grams (93% yield) of bis-(4-fluoro-benzyl)-amine hydrochloride. MS (M+H) calcd for C14H14F2N, 234.1. found: 234.0. Anal. calcd for C14H14F2NCl: C, 62.34; H, 5.23; N, 5.19. found: C, 61.89; H, 5.15; N, 5.27. 1H NMR (500 MHz, DMSO) δ: 4.12 (br s, 4), 7.26 (m, 4), 7.65 (m, 4), 9.91 (br s, 2).

Workup

  1. temperaturethe resulting mixture heated
  2. temperatureto reflux for 15 min
  3. temperatureto warm to room temperature
  4. customThe reaction flask was fitted with a distillation condenser
  5. customsolvent removed
  6. temperatureunder reflux for 25 min
  7. customThe distillation apparatus was replaced with a reflux condenser
  8. temperaturethe reaction heated to 110° C. for 2 h
  9. temperatureAfter cooling to 0° C.
  10. addition100 mL of 6N HCl was added
  11. temperaturethe mixture heated
  12. temperatureto reflux for 1 hr
  13. customto yield a thick slurry
  14. temperaturewith intermittent cooling
  15. additionwas added
  16. customthe mixture transferred to a separatory funnel
  17. customThe organic layer was separated
  18. dry with materialdried over Na2SO4
  19. filtrationfiltered
  20. customthe solvent removed under vacuum
  21. customto yield an oil
  22. customresulting in the formation of a white precipitate which
  23. customwas isolated by filtration

Sources & evidence

ORD record
ord-508233b4973b4d72bc9b5d9f4ac30584
Source dataset
uspto-grants-2006_09
Patent number
US07109186B2

Reaction notes

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