Benzo(B)Thiophene-2-Boronic Acid → HCID 68683394, compound

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Reaction Steps

A mixture of (−)-8-methyl-3-(trifluoromethylsulfonyloxy)-8-azabicyclo[3.2.1]oct-2-ene, (4.64 g, 17.1 mmol), 1,2-dimethoxyethane (100 ml), 2-benzothienyl boronic acid (4.5 g, 25 mmol), potassium carbonate (9.2 g, 66.6 mmol), lithium chloride (2.0 g, 47.2 mmol) and water (50 ml) was bubbled through with argon for 10 min. Pd(PPh3)4 (0.17 g, 0.13 mmol) was added followed by reflux for 45 min. The mixture was allowed to cool to room temperature. Water (100 ml) was added followed by extraction with diethyl ether (2×50 ml). The organic phase was washed with water (2×50 ml). The organic phase was dried and evaporated. The hydrochloric acid salt was precipitated by addition of hydrochloric acid (4 M) solved in ethanol (5 ml, 96%). Addition water (50 ml) and concentrated ammonia (50 ml) followed by extraction with dichloromethane (2×50 ml) gave the free base. (4.09 g, 100% from the salt) [α]D25=(−)-46.3°. The tartaric acid salt was prepared by adding D-tartaric acid (2.4 g, 16 mmol) to a mixture of the free base and ethanol (96%) at reflux. The mixture was allowed to cool overnight and was isolated by filtration. Yield 5.06 g (12.47 mmol), chiral HPLC (−) 94.9% and (+) 5.1%. Recrystallization of 4.85 g (11.9 mmol) from ethanol (150 ml, 96%) yielded (3.26 g, 8.0 mmol), chiral HPLC (−) 97.9% and (+) 2.1%. Mp 67.6-76.0° C.

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