1-(4-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)piperidin-2-one synthesis

Yield:1007346-42-0 36.1%

Reaction Conditions:

Stage #1: 5-bromovaleroyl chloride;4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)anilinewith triethylamine in dichloromethane at 0 - 20; for 18.5 h;
Stage #2: with sodium hydride in N,N-dimethyl-formamide;mineral oil at 0 - 20; for 21 h;

Steps:

95.1

Step 1: Preparation of 1-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]piperidin-2-one Et₃N (239 μL, 1.71 mmol) and 5-bromovaleroyl chloride (166 μL, 1.26 mmol) were added to a solution of 4-aminophenylboronic acid pinacol ester (250 mg, 1.14 mmol) in DCM (5 mL) at 0° C. After stirring the mixture for 18.5 hours at room temperature, the mixture was concentrated. The residue was diluted with EtOAc and washed with sat. NaHCO₃ and brine. The organic layer was dried over anhydrous Na₂SO₄, and concentrated. The residue was diluted with DMF (5 mL) and NaH (55% in liquid paraffin, 62.2 mg, 1.43 mmol) at 0° C. After stirring the mixture for 21 hours at room temperature, the mixture was concentrated. The residue was diluted with 10% aqueous citric acid and extracted with DCM (3*). The combined organic layers were dried over anhydrous Na₂SO₄, and concentrated. The residue was purified by PTLC (EtOAc/hexane=1:1) to afford desired product (124 mg, 36.1%) as white solid. ¹HNMR (CDCl₃) 400 MHz δ: 7.86-7.81 (m, 2H), 7.30-7.24 (m, 2H), 3.70-3.60 (m, 2H), 2.61-2.51 (m, 2H), 2.00-1.87 (m, 4H), 1.33 (s, 12H).

References:

US2012/108574,2012,A1 Location in patent:Page/Page column 138