Potassium Carbonate → 3-(4-Methyl-3-oxo-7-phenyl-2,3,4,10-tetrahydro-9-oxa-1,2,4a-triaza-phenanthren-6-ylamino)-azetidine-1-carboxylic acid tert-butyl ester

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A mixture of 3-(7-bromo-4-methyl-3-oxo-2,3,4,10-tetrahydro-9-oxa-1,2,4a-triaza-phenanthren-6-ylamino)-azetidine-1-carboxylic acid tert-butyl ester (1 g, 2.1 mmol), phenylboronic acid (0.79 g, 6.4 mmol), 1,1′-bis(diphenylphosphino)ferrocene-palladium(II)dichloride dichloromethane complex (0.351 g, 0.43 mmol) and K2CO3 (0.890 g, 6.4 mmol) in dioxane (24 mL) and water (4 mL) was heated at 110° C. overnight. The reaction mixture was cooled to ambient temperature and the solvent was removed in vacuo to give the crude product, which was purified by column chromatography (eluting with 10-40% EtOAc in petroleum ether) to give 3-(4-methyl-3-oxo-7-phenyl-2,3,4,10-tetrahydro-9-oxa-1,2,4a-triaza-phenanthren-6-ylamino)-azetidine-1-carboxylic acid tert-butyl ester (0.710 g racemate, 1.5 mmol, 71%) as an off-white powder. The racemic material was further separated by chiral SFC (Table 2, Method 1) to give two isomers: 3-(4(R)-methyl-3-oxo-7-phenyl-2,3,4,10-tetrahydro-9-oxa-1,2,4a-triaza-phenanthren-6-ylamino)-azetidine-1-carboxylic acid tert-butyl ester (Enantiomer 1, SFC (Table 1, Method 1), Rt=3.374 min., 0.281 g, 0.61 mmol, 29%) and 3-(4(S)-methyl-3-oxo-7-phenyl-2,3,4,10-tetrahydro-9-oxa-1,2,4a-triaza-phenanthren-6-ylamino)-azetidine-1-carboxylic acid tert-butyl ester (Enantiomer 2, SFC (Table 1, Method 1), Rt=4.333 min., 0.252 g, 26%). LC/MS (Table 1, Method 2) Rt=1.25 min.; MS m/z: 464 [M+H]+.

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