Imidazole → HCID 15229755, compound

1,22-Docosanediol 1 (2.00 g, 5.84 mmol) and imidazole (0.817 g, 12.0 mmol) were placed in each of two nitrogen-purged 150 mL three-necked flasks fitted with a thermometer and magnetic stir bar. The flasks were resealed and purged with nitrogen. Dimethylformamide (40 mL) was added to each flask and the cloudy mixtures were heated until they became homogenous at 63° C. tert-Butyldimethylsilyl chloride (0.904 g, 6.00 mmol, in 10 mL DMF) was slowly added to the reaction mixture (the transfer was aided with an additional 5 mL of DMF) and the mixture was allowed to react for 24 hours at 60°-65° C. The solutions were cooled down to room temperature and filtered to recover starting material using water (25 mL) to aid in transfer. The filtrate was diluted with water (300 mL) and extracted with methylene chloride (500 mL). The organic layer was dried (Na2SO4) and concentrated. A very low mass balance led to the discovery that much of the desired material was contained in the recovered solid that had been previously filtered off. None of the desired compound was found in the aqueous wash by TLC. The recovered solid was suspended in methylene chloride (100 mL), stirred, and refiltered. The filtrate was combined with the previously isolated material and concentrated in vacuo. The crude material was purified by flash chromatography (silica gel, 10% ethyl acetate/hexane). Concentration of the desired fractions using acetone to reduce violent bumping yielded the desired material 2 as a white solid (2.22 g, 46.7%).

1. custompurged 150 mL three-necked flasks
2. customfitted with a thermometer and magnetic stir bar
3. custompurged with nitrogen
4. additionDimethylformamide (40 mL) was added to each flask
5. temperaturethe cloudy mixtures were heated until they
6. custombecame homogenous at 63° C.
7. additionwas slowly added to the reaction mixture (the transfer
8. customto react for 24 hours at 60°-65° C
9. filtrationfiltered
10. customto recover
11. additionThe filtrate was diluted with water (300 mL)
12. extractionextracted with methylene chloride (500 mL)
13. dry with materialThe organic layer was dried (Na2SO4)
14. concentrationconcentrated
15. filtrationhad been previously filtered off
16. washaqueous wash by TLC
17. concentrationconcentrated in vacuo
18. customThe crude material was purified by flash chromatography (silica gel, 10% ethyl acetate/hexane)

ORD record

ord-d7d18d09016046228deaa36281406d56

Source dataset

uspto-grants-1998_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05811568