Iodine → HCID 21034940, compound

3-Methoxybenzyl chloride (3.13 g, 20 mmol) was dissolved in 10 mL of diethyl ether and magnesium metal (0.49 g, 20.5 mmol) was added without stirring. Several crystals of iodine were added. After the reaction was initiated, stirring was begun and external cooling was applied as necessary to maintain gentle refluxing. Once the initial reaction had subsided, the mixture was refluxed×1 hour. The mixture was diluted to 40 mL with diethyl ether and cooled in an ice-bath. The etheral solution of (3-benzyloxy-4-methoxy-benzylidene)-(2,2-dimethoxy-ethyl)-amine was added dropwise to the cold solution. After the addition was complete, the resulting suspension was heated at reflux×2 hours. The mixture was cooled in an ice-bath and saturated aqueous ammonium chloride solution (20 mL) was added dropwise. The mixture was stirred at 0° C.×15 minutes and then at room temperature×1 hour. Water (20 mL) was added, and the mixture was filtered. The organic layer was separated, washed with water (1×20 mL), saturated aqueous sodium chloride solution (1×20 mL) and dried over anhydrous magnesium sulfate. The solvent was concentrated in vacuo to give a viscous oil. The oil was dissolved in tetrahydrofuran (20 mL) and water (10 mL) was added. Then potassium carbonate (2.5 g) was added at room temperature followed by dropwise addition of ethyl chloroformate (1.08 g, 10 mmol, 0.95 mL). The mixture was stirred×1 hour at room temperature. The mixture was diluted with diethyl ether (50 mL), and the organic layer was separated and dried over anhydrous magnesium sulfate. The solvent was concentrated in vacuo. The resulting viscous oil was used purified by silica gel chromatography (25% to 35% ethyl acetate in hexanes to give [1-(3-Benzyloxy-4-methoxy-phenyl)-2-(3-methoxy-phenyl)-ethyl]-(2,2-dimethoxy-ethyl)-carbamic acid ethyl ester (4.51 g, 8.6 mmol, 86%) as pale yellow viscous oil.

1. stirringstirring
2. temperatureexternal cooling
3. temperatureto maintain gentle refluxing
4. customOnce the initial reaction
5. temperaturethe mixture was refluxed×1 hour
6. temperaturecooled in an ice-bath
7. additionAfter the addition
8. temperaturethe resulting suspension was heated
9. temperatureat reflux×2 hours
10. temperatureThe mixture was cooled in an ice-bath
11. stirringThe mixture was stirred at 0° C.×15 minutes
12. customat room temperature
13. custom×1 hour
14. filtrationthe mixture was filtered
15. customThe organic layer was separated
16. washwashed with water (1×20 mL), saturated aqueous sodium chloride solution (1×20 mL)
17. dry with materialdried over anhydrous magnesium sulfate
18. concentrationThe solvent was concentrated in vacuo
19. customto give a viscous oil
20. stirringThe mixture was stirred×1 hour at room temperature
21. customthe organic layer was separated
22. dry with materialdried over anhydrous magnesium sulfate
23. concentrationThe solvent was concentrated in vacuo
24. customThe resulting viscous oil was used purified by silica gel chromatography (25% to 35% ethyl acetate in hexanes

ORD record

ord-1c1dfda1026b41d79275ce040a21e426

Source dataset

uspto-grants-2006_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07067529B2