Alcohol to Fluoride

(DAST)

Examples:

Example 1

To a solution of the SM (3.3 g, 32.3 mmol) in DCM (100 mL) at -78 C under N2 was added DAST (13.0 mL, 96.9 mmol). The reaction mixture was stirred at -78 C for 1 h, then at RT for 1 h. The reaction mixture was then slowly poured into sat aq NaHCO3 (200 mL) at 0 C. The mixture was extracted with DCM (2 x 60 mL). The combined organics were dried (Na2SO4) and concentrated. The residue was purified by silica gel column chromatography (10:1 PE/EtOAc) to provide the product as a colorless oil. [2.2 g, 65%]

[Patent Reference: WO2016011390, page 382, (20.2 MB)]

Example 2

To a solution of the SM (1.04 g, 4.5 mmol) in DCM (20 mL) was added dropwise DAST (1.09 g, 6.8 mmol) at 0 C. The reaction mixture was stirred at RT for 90 min. The mixture was quenched with sat aq NaHCO3 (40 mL), extracted with DCM (40 mL), dried (Na2SO4), and concentrated. The residue was purified by silica gel column chromatography (25:1 PE/EtOAc) to provide the product as a yellow oil. [470 mg, 45%]

[Patent Reference: WO2016011930, page 160, (15.7 MB)]

Example 3

The SM (0.18 g, 0.44 mmol) was dissolved in DCM (10 mL) and cooled to -78 C. DAST (0.14 g, 0.88 mmol) was added dropwise and the reaction mixture was stirred at RT for 12 h. The mixture was poured into H2O, neutralized with sat aq NaHCO3, and extracted with EtOAc. The org layer was washed with brine, dried (Na2SO4), and concentrated. The residue was purified by silica gel column chromatography (25-30 % EtOAc/hexane) to provide the product. [0.08 g, 45%]

[Patent Reference: WO2015164458, page 90, (6.0 MB)]