Methanesulfonyl chloride → 2-Pyridinepropanol, 6-methoxy-, 2-methanesulfonate

Temperature

-78 °C

To a solution of 2-bromo-6-methoxypyridine (144-1, 1.6 g, 8.88 mmol) in THF (30 mL) at −78° C. was added a 2.5 molar solution of n-Butyllithium in THF (3.9 mL, 5.86 mmol) and the system was stirred at −78° C. for 20 minutes followed by the addition of (3-bromopropoxy)(tert-butyl)dimethylsilane (1.5 g, 5.92 mmol). After 1 h, the cold bath was removed and the system was stirred as it approached ambient temperature. The contents were extracted with water and EtOAc. The organic phase was dried over MgSO4, filtered, concentrated and purified by gradient elution on silica (0 to 10% EtOAc in Hx) to afford afford a pale yellow oil. To this pale yellow oil (1.5 g, 5.33 mmol) in THF (26 mL) was added a 1.0 molar solution of tetrabutylammoniumfluoride in THF (10.0 mL, 10.7 mmol) and the system was stirred for 1 h. The reaction contents were concentrated in vacuo and the resulting residue was purified by gradient elution on silica (0 to 100% EtOAc in Hx) to afford a pale yellow oil. To this pale yellow oil (0.3 g, 1.80 mmol) in DCE (9 mL) at 0° C. was added methanesulfonylchloride (0.17 mL, 2.16 mmol) and the system was stirred for 15 minutes at 0° C. The reaction contents were extracted with water and EtOAc. EtOAc. The organic phase was dried over MgSO4, filtered and concentrated to afford 144-2 as a pale yellow oil. ESI+ MS C10H15NO4S: 246.1 found, 246.1 required.

1. waitAfter 1 h
2. customthe cold bath was removed
3. stirringthe system was stirred as it
4. customapproached ambient temperature
5. extractionThe contents were extracted with water and EtOAc
6. dry with materialThe organic phase was dried over MgSO4
7. filtrationfiltered
8. concentrationconcentrated
9. custompurified by gradient elution on silica (0 to 10% EtOAc in Hx)
10. customto afford
11. customafford a pale yellow oil
12. stirringthe system was stirred for 1 h
13. customThe reaction contents
14. concentrationwere concentrated in vacuo
15. customthe resulting residue was purified by gradient elution on silica (0 to 100% EtOAc in Hx)
16. customto afford a pale yellow oil
17. stirringthe system was stirred for 15 minutes at 0° C
18. customThe reaction contents
19. extractionwere extracted with water and EtOAc
20. dry with materialThe organic phase was dried over MgSO4
21. filtrationfiltered
22. concentrationconcentrated

ORD record

ord-8492e6f5e7c14040a361cdc7fe0afbbe

Source dataset

uspto-grants-2016_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09273033B2