Catecholborane → HCID 118307798, 화합물

참여 물질

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The benzo[d][1,3,2]dioxaborole (0.66 mL, 2.68 mmol; 50% soln in toluene) was added to a nitrogen purged solution of isopropyl 2-(5-bromo-4-(3-cyclopropylpyrrolidin-1-yl)-2,6-dimethylpyridin-3-yl)-2-oxoacetate (730 mg, 1.78 mmol) and 0.6 ml, of 1M (R)-1-methyl-3,3-diphenylhexahydropyrrolo[1,2-c][1,3,2]oxazaborole (148 mg, 0.54 mmol) in toluene (18 mL) cooled to −50° C. The reaction was allowed to slowly warm to −15° C. and placed in the freezer for 18 h before being quenched with 1M Na2CO3 (5 mL) and stirred for 20 min. The organic layer was washed with brine and dried (MgSO4). The crude product was charged (DCM) to a 40 g ISCO silica gel cartridge and gradient elution (5-50% EtOAc/hexanes) using an Isolera chromatography station gave (2S)-isopropyl 2-(5-bromo-4-(3-cyclopropylpyrrolidin-1-yl)-2,6-dimethylpyridin-3-yl)-2-hydroxyacetate 540 mg (74%) as a mixture of diastereomers; major isomer. 1H NMR (500 MHz, DMSO-d6) δ 5.52 (s, 1H), 4.96-4.89 (m, 1H), 3.40-3.35 (m, 2H), 3.17-3.09 (m, 1H), 2.94-2.90 (m, 1H), 2.53 (s, 3H), 2.40 (s, 3H), 2.03 (br. s., 1H), 1.82-1.74 (m, 2H), 1.17-1.08 (m, 6H), 0.76-0.75 (m, 1H), 0.43-0.41 (m, 2H), 0.15-0.14 (m, 2H). UPLC (M+H)=413.2.

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