background and overview[1]
4-bromobenzoylacetonitrile can be used as a pharmaceutical synthesis intermediate. it can be prepared from 3-bromobenzoic acid as the reaction raw material. the intermediate 3-bromobenzoic acid methyl ester is first prepared, and 4 is generated under the action of sodium cyanide. -bromobenzoylacetonitrile.
preparation[1]
step 1: methyl 3-bromobenzoate
to a mixture of 3-bromobenzoic acid (85.0 g, 423 mmol) in methanol (700 ml) was added dropwise thionyl chloride (151 g, 1.27 mol) under a nitrogen atmosphere at room temperature. the mixture was stirred at 62°c for 16 hours. upon completion, the reaction was concentrated in vacuo to give a residue. the residue was washed with saturated sodium bicarbonate (100 ml) and extracted with dichloroethane (2 x 100 ml). the organic layer was dried over sodium sulfate and concentrated in vacuo to give the title compound. 1hnmr (mhz, cdcl3) δ=8.21 (s, 1h), 8.09-7.90 (m, 1h), 7.78-7.61 (m, 1h), 7.46 -7.21 (m, 1h), 3.97 (s, 3h).
step 2: 4-bromobenzoylacetonitrile
under nitrogen atmosphere, add sodium hydride (6.05g, 151mmol) in portions to a mixture of acetonitrile (7.78g, 190mmol, 9.97ml) and anhydrous tetrahydrofuran (300ml) at room temperature, and then add 3-bromobenzene methyl formate (25.0 g, 116 mmol) was added to the mixture, and the resulting mixture was heated to 77 °c and stirred for 2 hours. after completion, the reaction was cooled to room temperature, and hydrochloric acid solution (1n, ml) was added to the reaction. the aqueous layer was extracted with ethyl acetate (4 × 250ml), and the organic layer was washed with sodium bicarbonate (1.0l) and washed with sodium sulfate. dry and concentrate in vacuo to give the title compound 4-bromobenzoylacetonitrile. 1hnmr (mhz, cdcl3) δ=8.07 (brs, 1h), 7.94-7.76 (m, 2h), 7.44 (t, j=7.6hz, 1h ), 4.10 (s, 2h).
references
[1] wo2017156179 – 3-phosphoglycerate dehydrogenase inhibitors and uses thereof