Alcohol to Bromide

(Appel Reaction)

Examples:

Example 1

The SM (6.8 g, 0.036 mol) was taken up in DCM (275 mL) and treated with PPh3 (10.36 g) and CBr4 (13.1 g). The reaction mixture was stirred at RT for 90 min, after which time the solvent was concentrated to a volume of about 50 mL (precipitation occurs). The slurry was added to a pad of silica gel eluting with 20% EtOAc/hexane. Fractions containing the product (least polar) were combined and concentrated to provide the product as a viscous syrup. [6.2 g, 69%]

[Patent Reference: WO2014152144, page 56, (4.6 MB)]

Example 2

To a solution of PPh3 (26.2 g, 0.10 mol) in ACN (50 mL) at 0 C was added dropwise a solution of Br2 (5.13 mL, 0.10 mol) in ACN (30 mL). The SM (5.1 g, 0.050 mol) was added portionwise to the mixture and the reaction was stirred at 90 C for 16 h. The mixture was concentrated and the resulting material was suspended in MTBE (150 mL). The solids were removed by filtration and the filtrate was concentrated. The resulting residue was dissolved in ACN and extracted with hexane (3 x 100 mL). The combined hexane extracts were concentrated in vacuo to provide the product as a brown oil. [6.5 g, 59%]

[Patent Reference: WO2015129926, page 100, (21.5 MB)]

Example 3

To a solution of the SM (0.261 g, 0.987 mmol) in DCM at 0 C was added NBS (0.211 g, 1.19 mmol), followed by PPh3 (0.311 g, 1.19 mmol). The reaction mixture was stirred at 0 C for 1 h, after which time it was concentrated in vacuo (without warming). The crude material was purified by silica gel flash chromatography to provide the product as a white solid. [0.22 g, 68%]

[Patent Reference: WO2016014463, page 117, (6.7 MB)]

Example 4

To a solution of the SM (9.50 g, 36.1 mmol) and DIEA (9.43 mL, 54.1 mmol) in DCM (200 mL) was added PPh3Br2 (23.79 g, 54.11 mmol) at 0 C. The reaction mixture was stirred for 1 h, then concentrated in vacuo. The resulting residue was purified by silica gel chromatography to provide the product as a white solid. [8.74 g, 74%]

[Patent Reference: WO2016014463, page 88, (6.7 MB)]