Tetrabutylammonium Fluoride → HCID 11307291, compound

Participants

Reaction Steps

To a solution of 0.033 g of 4-(3′-cyano-biphenyl-4-yl)-4-[5,6-difluoro-1-(2-trimethylsilanyl-ethoxymethyl)-1H-benzoimidazol-2-ylmethoxy]-piperidine-1-carboxylic acid tert-butyl ester 62 (0.05 mmol, 1 eq) in 2.5 mL of tetrahydrofuran was added 0.10 mL tetrabutylammonium fluoride (1M in THF, 0.1 mmol, 2 eq). The reaction was stirred at room temperature for 20 h and then at 60° C. for 5 h. The mixture was allowed to cool to room temperature and then partitioned between 25 mL of ethyl acetate and 20 mL of H2O. The organic layer was separated, washed with saturated brine, dried (Na2SO4), and concentrated to give the crude product which was purified by flash silica gel chromatography eluting with a gradient of 10-50% ethyl acetate in hexane to yield 0.025 g of the desired product 4-(3′-cyano-biphenyl-4-yl)-4-(5,6-difluoro-1H-benzoimidazol-2-ylmethoxy)-piperidine-1-carboxylic acid tert-butyl ester 63 as a pale foam: 1H NMR (300 MHz, CDCl3): δ 9.96 (br. s., 1H), 7.82-7.81 (m, 1H), 7.78-7.75 (dt, 1H), 7.65-7.61 (m, 1H), 7.57-7.40 (m, 6H), 7.30-7.24 (m, 1H), 4.43 (s, 2H), 4.00 (d, 2H), 3.31-3.23 (t, 2H), 2.24-2.19 (d, 2H), 2.07-1.97 (td, 2H), 1.48 (s, 9H); MS (ESI): Calcd m/z for C31H30F2N4O3.H+=545.2. Found m/z=545 (M+1)+.

Provenance & Evidence