3-FLUOROPROPYL-1-METHANESULFONATE synthesis

Yield:372-04-3 93.6%

Reaction Conditions:

with sulfuryl dichloride;triethylamine in dichloromethane at 0 - 5; for 2 h;

Steps:

A solution of methanesulfonyl chloride (1.714 ml, 22.00 mmol) in DCM (5 ml) was added dropwise to a stirred cold (0 ⁰C) solution of 3-fluoropropan-l-ol (1.562 g, 20 mmol) and TEA (3.35 ml, 24.00 mmol) in DCM (20 ml). The mixture was stirred at 0-5 ⁰C for ~2 h and washed with water, satd. NaHCO3, water, brine and dried (MgSO4). Evaporation of DCM gave 3-fluoropropyl methanesulfonate as a colorless oil (2.92 g, 93.6%). Neat potassium thioacetate (2.74 g, 24.00 mmol) was added to a stirred solution of 3-fluoropropyl methanesulfonate (2.9 g) in DMSO (20 ml) and the mixture stirred overnight. Product was extracted with ether (2X25 ml), washed with water, brine and dried (MgSO4). Evaporation of ether gave S-3- fluoropropyl ethanethioate as a light brown oil. Chlorine gas was bubbled into cold (- 10 ⁰C) stirred two-phase solution of S-3-fluoropropyl ethanethioate (1.0 g, 7.34 mmol) in DCM (5 ml) and Water (5.00 ml) until green color appeared in aqueous phase and maintained for 1-2 h. Layers separated and aq. layer re-extracted with DCM (2X10 ml). Combined DCM extracts were washed with 10% NaHSO3 solution, water, brine and dried (MgSO4). Evaporation of DCM gave the intermediate, 3-fluoropropane-l-sulfonyl chloride as a light brown oil (405 mg, 34%) which was treated with an. NH3 solution (10 ml, 0.5M in dioxane) and stirred for 30- 45 min. Precipitated NH4C1 was filtered off and the filtrate was evaporated to dryness to afford 3 -fluoropropane-1 -sulfonamide as a light brown oil (265 mg).

References:

WO2009/67108,2009,A1 Location in patent:Page/Page column 133-134