Sodium triacetoxyborohydride → (1R,5S,6R)-5-(5-((cyclobutylmethyl)amino)-2-fluorophenyl)-5-(difluoromethyl)-2-oxa-4-azabicyclo[4.1.0]hept-3-en-3-amine

Participants

Reaction Steps

To a solution of (1R,5S,6R)-5-(5-amino-2-fluorophenyl)-5-(difluoromethyl)-2-oxa-4-azabicyclo[4.1.0]hept-3-en-3-amine (16g-B, 50 mg, 0.184 mmol) in 1,2-dichloroethane (1.2 mL) was added cyclobutanecarbaldehyde (15.51 mg, 0.184 mmol) and sodium triacetoxyborohydride (0.033 mL, 0.221 mmol). After addition, the mixture was then stirred at room temperature for 3 h. Additional cyclobutanecarbaldehyde (15.51 mg, 0.184 mmol) was added and the mixture was stirred at room temperature for additional 30 min. The mixture was quenched with saturated NaHCO3 and extracted with DCM (1×6 mL). The organic layer was collected, dried over MgSO4, and concentrated. The residue was then dissolved in MeOH and solution mixture was purified by preparative HPLC (0%-100% MeCN 0.1% TFA/H2O 0.1% TFA) to give a desired product, which was dissolved in MeOH. The solution was loaded onto a PL-HCO3 MP SPE 200 mg/6 mL column and eluted with MeOH (2×2 mL). The combined eluates were concentrated and dried in vacuo to give 30 mg of the title compound as a light yellow solid. MS m/z=340.1 [M+H]+

Provenance & Evidence