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

Participants

Reaction Conditions

Reaction Steps

The 1.3 mL of benzo[d][1,3,2]dioxaborole (709 mg, 5.91 mmol) was added to a nitrogen purged solution of isopropyl 2-(4-(4-benzylpiperidin-1-yl)-5-bromo-2,6-dimethylpyridin-3-yl)-2-oxoacetate (1.4 g, 2.96 mmol) and 1.2 mL of (R)-1-methyl-3,3-diphenylhexahydropyrrolo[1,2-c][1,3,2]oxazaborole (328 mg, 1.18 mmol) in toluene (30 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, diluted with EtOAc, and stirred for 30 min. The organic layer was washed with sat'd Na2CO3 solution, brine and dried (MgSO4). The crude product was charged (DCM) to a 80 g ISCO silica gel cartridge and gradient elution (0-50% EtOAc/hexanes) using an Isolera chromatography station gave (S)-isopropyl 2-(4-(4-benzylpiperidin-1-yl)-5-bromo-2,6-dimethylpyridin-3-yl)-2-hydroxyacetate as a mixture of diastereomers 1.4 g (100%). 1H NMR (500 MHz, DMSO-d6) δ 7.30-7.27 (m, 2H), 7.19-7.18 (m, 3H), 5.95/5.93 (s, 1H), 4.97-4.93 (m, 1H), 3.53 (t, J=11.4 Hz, 1H), 3.40-3.38 (m, 1H), 3.31 (t, J=11.7 Hz, 1H), 3.25 (br. s, 1H), 2.87 (d, J=10.3 Hz, 1H), 2.77 (d, J=10.6 Hz, 1H), 2.55/2.54 (s, 3H), 2.38 (s, 3H), 1.60-1.52 (m, 3H), 1.38-1.63 (m, 2H), 1.14 (d, J=5.9 Hz, 3H), 1.05 (d, J=5.9 Hz, 3H). UPLC (M+H)=477.1.

Provenance & Evidence