Ethanol → HCID 57738060, compound

Participants

Reaction Conditions

Reaction Steps

A 3 L round-bottom flask was fitted with a mechanical overhead stirrer, a reflux condenser, and a thermometer and purged with N2. 3-Fluoro-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine (2) (95.0 g, 421 mmol, 1.2 equiv), 4-bromo-2-nitro-6-(pyrimidin-2-yl)benzenamine (3) (104.55 g, 354 mmol, 1.0 equiv), K3PO4 (93.1 g, 438 mmol, 1.25 equiv, Riedel-deHaen #S29375-366), Pd(OAc)2 (0.80 g, 3.5 mmol, 1 mol %, Aldrich #06410JE) cetyltrimethylammonium bromide (1.28 g, 3.5 mmol, 1 mol %, Aldrich #0823CE) and PPh3 (3.74 g, 14 mmol, 4 mol %, Fluka #1093859) were added followed by EtOH (10 vols) and water (1.1 vols). The heterogeneous reaction mixture was stirred vigorously (>300 rpm) and heated to reflux (80° C.). After 6 hours a sample was removed for analysis of reaction completion (method C). After the reaction was judged complete, the mixture was cooled to 30° C., then water (10 vol) was added and the reaction stirred for 2 h. The resulting slurry was filtered and the filter cake washed with water (2×5 vol) and acetonitrile (2×5 vol). The filter cake was then charged back to the flask and water added (10 vol). The slurry was stirred for 3 h at 30° C. and filtered again. The filter cake was then transferred to a dish and allowed to dry under vacuum at 60-80° C. for 12 h furnishing compound (4) as an orange powder (104.87 g, 88%, purity: 96.14% AUC determined using method A). Typical reaction times were 7.9 min for SM (2) and 6.9 min for product (4).

Provenance & Evidence