Water → (3-(8-Chloroimidazo[1,5-a]pyrazin-3-yl)cyclobutyl)methanol

Participants

Reaction Steps

To a solution of 8-chloro-3-(3-methylenecyclobutyl)imidazo[1,5-a]pyrazine (4.48 g, 20.4 mmol) in anh THF (255 mL) at −78° C. under Ar, 9-BBN (61.2 mL, 0.5M in THF, 30.6 mmol) was added dropwise over 8 min (a suspension). The cooling bath was replaced with ice-H2O and the reaction was allowed to warm slowly to rt. After being stirred for 17 h, H2O (100 mL) was added followed by, after ˜5 min, NaBO3.H2O (12.2 g, 122.3 mmol) added in one lot. The reaction was stirred at rt for 5 h and then filtered through Celite. The Celite and residual solids were washed with DCM and EtOAc. The filtrate was concentrated under reduced pressure to yield an aq solution, which was saturated with NaCl and extracted with EtOAc (3×). The extracts were dried (Na2SO4) and concentrated under reduced pressure to yield a light yellow oil which was purified by flash chromatography on SiO2 (9:1 DCM:MeOH) to afford the title compound as a light yellow oil; HPLC: tR (mass-directed HPLC, polar 7 min) 2.52 min; MS (ES+): 238.0. The addition may be carried out at 0° C. Suspension quickly clears up after the exchange of cooling baths. The final product contained 1,5-cis-octanediol derived from 9-BBN. Based on 1H NMR estimated roughly to be 66% target material and 33% of the byproduct. The crude product was taken onto next step crude, stereoselectivity of the product was 4-5:1 as judged by 1H NMR.

Provenance & Evidence