Catecholborane → (S)-isopropyl 2-(5-bromo-4-(4-(3-isopropyl-1,2,4-oxadiazol-5-yl)piperidin-1-yl)-2,6-dimethylpyridin-3-yl)-2-hydroxyacetate

Beteiligte Stoffe

Reaktionsbedingungen

Reaktionsschritte

The 1.6 mL of benzo[d][1,3,2]dioxaborole (416 mg, 3.47 mmol) was added to a nitrogen purged solution of isopropyl 2-(5-bromo-4-(4-(3-isopropyl-1,2,4-oxadiazol-5-yl)piperidin-1-yl)-2,6-dimethylpyridin-3-yl)-2-oxoacetate (950 mg, 1.93 mmol) and 0.6 mL of (R)-1-methyl-3,3-diphenylhexahydropyrrolo[1,2-c][1,3,2]oxazaborole (160 mg, 0.58 mmol) in toluene (20 mL) at −60° C. and allowed to warm to −15° C. before being placed in the freezer overnight. The reaction was quenched with 1M Na2CO3 (5 mL), diluted with EtOAc, and stirred for 20 min. The organic layer was washed with brine and dried (MgSO4). The crude product was filtered, and charged (DCM) to a 40 g ISCO silica gel cartridge and gradient elution (5-60% EtOAc/hexanes) using an Isolera chromatography station gave (S)-isopropyl 2-(5-bromo-4-(4-(3-isopropyl-1,2,4-oxadiazol-5-yl)piperidin-1-yl)-2,6-dimethylpyridin-3-yl)-2-hydroxyacetate 550 mg (58%) as a mixture of diastereomers. 1H NMR (500 MHz, DMSO-d6) δ 5.98/5.87 (s, 1H), 4.95-4.92 (m, 1H), 3.75-3.71 (m, 1H), 3.08-3.01 (m, 3H), 2.88-2.86 (m, 1H), 2.54 (s, 3H), 2.39 (s, 3H), 2.06-2.00 (m, 3H), 1.90-1.83 (m, 2H), 1.27 (d, J=6.6 Hz, 6H), 1.14 (d, J=5.9 Hz, 3H), 1.08 (d, J=5.9 Hz, 3H). UPLC (M+H)=497.2.

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