Iodine → HCID 22004984, compound

Participants

Reaction Steps

A dry flask containing freshly ground magnesium turnings (2.88 g, 120 mmol) and a crystal of iodine was heated until a dark purple iodine atmosphere had formed. The flask was cooled to ambient temperature and a solution of 2-bromo-5-fluorophenyl benzyl ether (33.8 g, 120 mmol, Example 166, Step A) in dry tetrahydrofuran (60 mL) was added in several portions over 40 minutes at a rate sufficient to maintain reflux. Reflux was continued for 45 minutes, then the reaction was cooled to room temperature. This solution of Grignard reagent was transferred via syringe to a second flask containing a solution of the intermediate from Step D (11.0 g, 30.2 mmol) in dry benzene (66 mL). The reaction mixture was held at reflux for one hour, quenched with 10% aqueous hydrochloric acid (300 mL) and extracted with diethyl ether (3×300 mL). The combined extracts were dried over magnesium sulfate and concentrated in vacuo to give a brown oil which was subjected to flash column chromatography on silica (80 mm×19.5″) using a stepwise gradient elution of dichloromethane:hexanes (1:3, 1:2, 1:1, 4L each). The fractions containing the product were combined and concentrated to afford an inseparable mixture of the product and an unidentified side product in about a 1:1 ratio as a pale yellow gum (5.3 g, 33% mass balance). This material was not fully characterized and was used without further purification.

Provenance & Evidence