3-Bromopyridine → HCID 68058278, compound

Participants

Reaction Conditions

Reaction Steps

To a magnetically stirred solution of 2,2,6,6-tetramethylpiperidine (2.50 g, 17.70 mmol) in dry THF (80 mL) under argon at −78° C. was slowly added over 2 min n-butyllithium (2.50 M in hexanes; 5.6 ml, 14.0 mmol). The reaction mixture was stirred at −78° C. for 5 min and then allowed to warm to about 0° C. over 10 min. The reaction mixture was cooled to −78° C. and slowly over 10 min was added dropwise neat 3-bromopyridine (1.335 ml, 13.61 mmol). The reaction mixture was stirred at −78° C. for 15 min, and then slowly treated with neat oxetan-3-one (870 mg, 12.07 mmol) over 2-3 min. The reaction mixture was then allowed to warm to room temperature slowly over 18 h. The reaction mixture was concentrated in vacuo, then partitioned with ethyl acetate/aqueous saturated NH4Cl and solid sodium bicarbonate until pH ˜8-9 was achieved. The aqueous layers were saturated with sodium chloride and back extracted with ethyl acetate. The organic layers were combined, washed with brine, dried over Na2SO4, filtered, and evaporated to dryness to give a red oil. The crude material was purified by Biotage Silica gel chromatography on a 80 g Thompson Single Step™ silica cartridge using a linear gradient from 100% CH2Cl2 to 100% ethyl acetate over 12 column volumes to give to give 860 mg (31%) of the title compound as a white solid. 1H NMR (500 MHz, CDCl3) δ ppm 8.75 (1 H, s), 8.58 (1 H, d, J=5.0 Hz), 7.24 (1 H, d, J=5.0 Hz), 5.16 (2 H, m), 4.91 (2 H, m), 3.12 (1 H, br.s). LC/MS (Condition B): ret. T=1.1 min, (M+H)+ 229.89, 231.89.

Provenance & Evidence