Imidazole → HCID 49820308, compound

Temperature

0 °C

To a solution of 3 (10.0 g, 38.43 mmol) in pyridine (50 mL) were added dichloromethane (50 mL). The solution was cooled to 0° C. To the solution was added 4,4′-dimethoxytrityl chloride (14.32 g, 42.27 mmol) and the solution was stirred at 0° C. for 5 h. Methanol (5 mL) was added to quench the reaction. The solution was concentrated to dryness under reduced pressure and the residue was partitioned between ethyl acetate (500 mL) and water (50 mL). The organic solution was washed with brine (50 mL) and dried (sodium sulfate, 4 g). The solvent was removed under reduced pressure and the residue was dissolved in dichloromethane (100 mL). To the solution were added imidazole (7.83 g, 115 mmol) and t-butyldimethylsilyl chloride (8.68 g, 57.6 mmol). The solution was stirred at ambient temperature for 16 h. Methanol was added to quench the reaction (5 mL) and the solvent was removed under reduced pressure and the residue was partitioned between ethyl acetate (500 mL) and water (50 mL). The organic solution was dried (sodium sulfate, 4 g) and evaporated under reduced pressure. The residue was purified by column chromatography (10-40% EtOAc in Hexane) to give 5′-β-DMT-3′-O-tBDMS intermediate product. This is turn was treated with 1% trifluoroacetic acid in dichloromethane (200 mL). The solution was stirred at ambient temperature for 1 h. Water (20 mL) was added and the solution was stirred at ambient for another 1 h. Methanol (5 mL) was slowly added and the solution was stirred at ambient for another 1 h. Ammonium hydroxide was added to adjust the solution pH to 7. The organic solution was separated, dried (sodium sulfate, 4 g) and evaporated to dryness under reduced pressure. The residue was purified by silica gel column chromatography (1-5% methanol in dichloromethane) to give 12 as a white solid 7.5 g in 50% yield over the three steps. 1H NMR (DMSO-d6) δ (ppm) 11.48 (br s, 1H, NH), 7.94 (d, 1H, H-6), 6.00 (d, 1H, H-1′), 5.69 (d, 1H, H-5), 4.06 (dd, 1H, 3′-H), 3.85 (m, 2H, H-5′a, H-4′), 3.58 (br d, 1H, H-5′ b), 1.27 (d, 3 H, 2-CH3), 0.89 (s, 9H, C(CH3)3), 0.12 (s, 6H, Si(CH3)2).

1. customto quench
2. customthe reaction
3. concentrationThe solution was concentrated to dryness under reduced pressure
4. customthe residue was partitioned between ethyl acetate (500 mL) and water (50 mL)
5. washThe organic solution was washed with brine (50 mL)
6. dry with materialdried (sodium sulfate, 4 g)
7. customThe solvent was removed under reduced pressure
8. dissolutionthe residue was dissolved in dichloromethane (100 mL)
9. stirringThe solution was stirred at ambient temperature for 16 h
10. customto quench
11. customthe reaction (5 mL)
12. customthe solvent was removed under reduced pressure
13. customthe residue was partitioned between ethyl acetate (500 mL) and water (50 mL)
14. dry with materialThe organic solution was dried (sodium sulfate, 4 g)
15. customevaporated under reduced pressure
16. customThe residue was purified by column chromatography (10-40% EtOAc in Hexane)
17. customto give 5′-β-DMT-3′-O-tBDMS intermediate product
18. stirringThe solution was stirred at ambient temperature for 1 h
19. stirringthe solution was stirred at ambient for another 1 h
20. stirringthe solution was stirred at ambient for another 1 h
21. customThe organic solution was separated
22. dry with materialdried (sodium sulfate, 4 g)
23. customevaporated to dryness under reduced pressure
24. customThe residue was purified by silica gel column chromatography (1-5% methanol in dichloromethane)

ORD record

ord-852b2f60542244f08569609f62e60dc0

Source dataset

uspto-grants-2014_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08633309B2