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

Participants

Reaction Conditions

Reaction Steps

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.

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