Alcohol to Fluoro / Carbonyl to Difluoro using DAST

General Procedure:

To a solution of alcohol or carbonyl compound (1 eq.) in dichloromethane (20 Vol) is added DAST (1.2 eq.) dropwise at –78 ^oC under nitrogen atmosphere and stirred at room temperature for 2 h. The reaction is monitored by TLC. The reaction mxture is quenched with saturated solution of NaHCO₃ and extracted with dichloromethane two times. The combined organic layer is successively washed with water (10 Vol x 2) and brine solution (5 Vol), dried over sodium sulphate, filtered and concentrated under reduced pressure. The crude product is purified by column chromatography.

Note:

• The most preferable solvent is DCM and the reaction is usually performed at 0 ^oC to -78 ^oC.

• DAST, (Diethylamino)sulfur trifluoride, is a nucleophilic fluorinating agent.

• DAST is heat sensitive and moisture sensitive. In general DAST reactions should not be heated.

• DAST is useful for dfluorination of carbonyl compounds as well

• Always look for safer alternatives to avoid DAST. There are several relatively safer reagents available to convert alcohol to fluoride

Safer alternatives to DAST:

• Deoxofluor — Relatively better

• Stable Fluorinating Reagent with Ease of Handling (FLUOLEAD^®) – A safer substitute for DAST

For more details on reactions and reagents, 
refer to the tab "Reaction, Reagents and Mechanism"

Typical Procedure:

• Fluorination of Alcohols Using DAST (TCI)

For more details on large-scale reactions and OPRD procedures, 
refer to the tab "Scale-up & Green Chem"

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