Pyridine → N-(((1S,3'R,4'S,5'S,6'R)-5-chloro-6-(4-ethylbenzyl)-3',4',5'-trihydroxy-3',4',5',6'-tetrahydro-3H-spiro[isobenzofuran-1,2'-pyran]-6'-yl)methyl)pivalamide

Participants

Reaction Steps

To a stirred solution of (1S,3′R,4′S,5′S,6′R)-6′-(aminomethyl)-5-chloro-6-(4-ethylbenzyl)-3′,4′,5′,6′-tetrahydro-3H-spiro[isobenzofuran-1,2′-pyran]-3′,4′,5′-triol (20 mg, 0.047 mmol) and 0.04 mL of pyridine in 1 mL of dichloromethane was added of pivaloyl chloride (60 μL, 0.05 mmol) and 3 mg of 4-dimethylaminopyridine. After being stirred for 2 h at ambient temperature, the reaction mixture was diluted with 20 mL of dichloromethane, washed with 1 M hydrochloric acid and concentrated. The residue was dissolved in 1 mL of methanol and cooled in an ice bath. After addition of 0.3 mL of 4 M potassium hydroxide solution, the mixture was stirred for 2 h at ambient temperature. The reaction mixture was then neutralized with 1 M hydrochloric acid and concentrated. The residue was partitioned between aqueous sodium hydrogen carbonate solution and ethyl acetate, and the organic layer was separated and dried over sodium sulfate. Concentration under reduced pressure provided the crude product, which was purified by preparative TLC to give 6.8 mg of title compound. 1H NMR (CD3OD, 300 MHz) δ 7.37 (s, 1H), 7.16 (s, 1H), 7.10 (s, 4H), 5.07 (s, 2H), 4.12 (d, J=15.8 Hz, 1H), 4.04 (d, J=15.8 Hz, 1H), 3.82-3.59 (m, 3H), 3.45-3.39 (m, 2H), 3.43 (dd, J=9.9, 8.4 Hz, 1H), 2.60 (q, J=7.6 Hz, 2H), 1.20 (t, J=7.6 Hz, 3H), 1.11 (s, 9H); MS ESI (m/z) 504 (M+1)+, calc. 503.

Provenance & Evidence