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

Participants

Reaction Conditions

Reaction Steps

The 0.7 mL of benzo[d][1,3,2]dioxaborole (396 mg, 3.3 mmol) was added to a nitrogen purged solution of isopropyl 2-(5-bromo-4-(3-isopropylazetidin-1-yl)-2,6-dimethylpyridin-3-yl)-2-oxoacetate (875 mg, 2.2 mmol) and 0.66 mL of (R)-1-methyl-3,3-diphenylhexahydropyrrolo[1,2-c][1,3,2]oxazaborole (183 mg, 0.66 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 charged (DCM) to a 80 g ISCO silica gel cartridge and gradient elution (5-35% EtOAc/hexanes) using an Isolera chromatography station gave (S)-isopropyl 2-(5-bromo-4-(3-isopropylazetidin-1-yl)-2,6-dimethylpyridin-3-yl)-2-hydroxyacetate 621 mg (71%) as a mixture of diastereomers. 1H NMR (500 MHz, DMSO-d6) δ 5.19 (d, J=4.4 Hz, 1H), 4.96-4.92 (m, 1H), 4.50 (t, J=8.1 Hz, 1H), 4.39 (t, J=8.4 Hz, 1H), 4.07 (t, J=7.0 Hz, 1H), 3.97 (t, J=7.3 Hz, 1H), 2.42 (s, 3H), 2.21 (s, 3H), 2.21-2.17 (m, 1H), 1.73-1.67 (m, 1H), 1.17 (d, J=6.2 Hz, 3H), 1.12 (d, J=6.2 Hz, 3H), 0.83 (d, J=6.6 Hz, 6H). UPLC (M+H)=401.3.

Provenance & Evidence