Lithium Hexamethyldisilazide → HCID 58465935, compound

Participants

Reaction Conditions

Reaction Steps

A vial was charged with (S)-7′-bromo-4′-fluoro-2′-methoxy-2,6-dihydrospiro[[1,4]oxazine-3,9′-xanthen]-5-amine (200 mg, 0.509 mmol), chloro(2-dicyclohexylphosphino-2′,6′-di-1-propoxy-1,1′-biphenyl)[2-(2-aminoethyl)phenyl] palladium(II) methyl-t-butylether adduct (18.53 mg, 0.025 mmol), 4,4-difluoropiperidine hydrochloride (160 mg, 1.017 mmol) and 1 ml of THF. The mixture was cooled to 0° C. and LHMDS (1M in THF) (2035 μL, 2.035 mmol) was added, and the vial was sealed and stirred at RT for 2 hr. At this point more chloro(2-dicyclohexylphosphino-2′,6′-di-i-propoxy-1,1′-biphenyl)[2-(2-aminoethyl)phenyl] palladium(II) methyl-t-butylether adduct (18.53 mg, 0.025 mmol), (18.53 mg, 0.025 mmol) was added followed by LHMDS solution (1 ml) and stirring continued for another hour. The mixture was quenched by addition of 2 ml of water and extracted with EtOAc. The combined organic fractions were concentrated and purified by chromatography [5-50% DCM/MeOH/NH4OH (90:10:1)] to afford (S)-7′-(4,4-difluoropiperidin-1-yl)-4′-fluoro-2′-methoxy-2,6-dihydrospiro[[1,4]oxazine-3,9′-xanthen]-5-amine as yellowish foam.

Provenance & Evidence