Iodination

(I2)

Examples:

Example 1

To a solution of the SM (28.0 g, 87.5 mmol) in DMF (270 mL) was added Iodine (24.42 g, 96.25 mmol) followed by KOH (12.17 g, 218.75 mmol). The mixture was stirred at RT for 1 h, after which time it was poured into ice with 5% sodium bisulfite. The aq layer was extracted with DCM and the combined organics were washed with H2O, dried, filtered, and concentrated. The residue was purified by silica gel chromatography (eluting with 2-3% MeOH/DCM) to provide the product. [23.2 g, 52.0 mmol] [WO2012129338, page 68]

Example 2

To a solution of the SM (400 mg, 2.46 mmol) in DMF (4.9 mL) was added Iodine (626 mg, 2.46 mmol) and KOH (346 mg, 6.17 mmol). The mixture was stirred at RT for 1 h, after which time it was poured into ice-H2O (30 mL) containing sodium bisulfite (257 mg, 2.46 mmol). The reaction was acidified with 5M HCl resulting in a yellow precipitate which was collected by filtration, washed with H2O, and dried overnight in a vac oven to provide the product. [516 mg, 72.6%] [WO2012129338, page 84]

Example 3

A brown solution of Iodine (3.98 g, 15.7 mmol) in DMF (4 mL) was added dropwise over 5 min to a yellow-brown suspension of the SM (2.5 g, 14.3 mmol) and K2CO3 (3.96 g, 28.7 mmol) in DMF (14 mL). The resulting mixture was stirred at RT for 16 h, after which time the reaction was added to mixture of ice (10 g), H2O (200 mL), and sodium bisulfite (2.23 g, 21.4 mmol). The resulting mixture was extracted with DCM (2 x 200 mL). The combined extracts were dried (Na2SO4) and concentrated to provide the product as a brown solid. [3.87 g, 90%] [WO2012129338, page 134]