Benzyl Bromide → Methyl N-(benzyloxycarbonyl)4-aminomethyl-2-O-benzylsalicylate

HRID 1956015Notes

Reaction equation

HRID 1956015 reaction equation
[CH2:1]([O:8][C:9]([NH:11][CH2:12][C:13]1[CH:14]=[C:15]([OH:23])[C:16](=[CH:21][CH:22]=1)[C:17]([O:19][CH3:20])=[O:18])=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH2:24](Br)[C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1.C(=O)([O-])[O-].[K+].[K+]>CC(C)=O>[CH2:1]([O:8][C:9]([NH:11][CH2:12][C:13]1[CH:14]=[C:15]([O:23][CH2:24][C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)[C:16](=[CH:21][CH:22]=1)[C:17]([O:19][CH3:20])=[O:18])=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 7498Benzyl BromideHCID 11430Potassium CarbonateHCID 54246052methyl N-(benzyloxycarbonyl)4-aminomethylsalicylate

Product 1

HCID 54469451Methyl N-(benzyloxycarbonyl)4-aminomethyl-2-O-benzylsalicylateYield 89.5%

Reagents, catalysts & solvents 1

HCID 180AcetoneSolvent

Procedure

Methyl N-(benzyloxycarbonyl )-4-aminomethylsalicylate (6.06 g, 19.2 mmoles) was dissolved in acetone (150 mL), and benzyl bromide (2.60 mL, 21.9 mmoles) and anhydrous potassium carbonate (13.28 g, 96.1 mmoles) were added. The mixture was stirred and heated at reflux for 22 hours. The mixture was concentrated to remove most of the acetone, and ethyl acetate (100 mL) was added. Aqueous hydrochloric acid (1N, 200 mL) was added slowly, swirling frequently to dissolve the solid carbonate. The layers were separated, and the aqueous layer was extracted with ethyl acetate (50 mL). The ethyl acetate solutions were combined and washed with water (100 mL) and saturated aqueous sodium chloride (50 mL), dried over anhydrous magnesium sulfate, filtered, and concentrated to about 50 mL. This solution was heated to boiling, and hexanes (150 mL) were added. The solution was cooled in ice, and crystals slowly formed. The crystals were collected by filtration, washed with hexanes, and dried in vacuo to afford 6.97 g (89% yield) of methyl N-(benzyloxycarbonyl)-4-aminomethyl-2-O-benzylsalicylate (m.p. 106°-107° C., open capillary, uncorrected).

Workup

  1. temperatureheated
  2. temperatureat reflux for 22 hours
  3. concentrationThe mixture was concentrated
  4. customto remove most of the acetone, and ethyl acetate (100 mL)
  5. additionwas added
  6. additionAqueous hydrochloric acid (1N, 200 mL) was added slowly
  7. dissolutionto dissolve the solid carbonate
  8. customThe layers were separated
  9. extractionthe aqueous layer was extracted with ethyl acetate (50 mL)
  10. washwashed with water (100 mL) and saturated aqueous sodium chloride (50 mL)
  11. dry with materialdried over anhydrous magnesium sulfate
  12. filtrationfiltered
  13. concentrationconcentrated to about 50 mL
  14. temperatureThis solution was heated
  15. additionhexanes (150 mL) were added
  16. temperatureThe solution was cooled in ice
  17. customcrystals slowly formed
  18. filtrationThe crystals were collected by filtration
  19. washwashed with hexanes
  20. customdried in vacuo

Sources & evidence

ORD record
ord-539bacaae0b74e4b81a8939d81124e6e
Source dataset
uspto-grants-1998_07
Patent number
US05777148

Reaction notes

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