Triethylamine → (3AR,5R)-5-((benzyloxy)methyl)-3a,4,5,7-tetrahydro-3H-pyrano[3,4-c]isoxazole

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Reaction Steps

A solution of 2-{[(2R)-1-(benzyloxy)pent-4-en-2-yl]oxy}-N-hydroxyethanimine (C4) (7.12 g, 28.6 mmol) in dichloromethane (168 mL) was placed in a room temperature water bath. Triethylamine (0.299 mL, 2.14 mmol) was added, followed by addition of bleach (aqueous sodium hypochlorite solution, 6.15%, 71 mL, 59 mmol) at a rate slow enough to maintain the internal reaction temperature between 22° C. and 25.5° C. Upon completion of the addition, the reaction mixture was diluted with water and extracted three times with dichloromethane. The combined organic extracts were washed with saturated aqueous sodium chloride solution, dried over sodium sulfate, filtered, and concentrated under reduced pressure. Purification via silica gel chromatography (Gradient: 0% to 35% ethyl acetate in heptane) provided the product as a yellow oil. The indicated relative stereochemistry of compound P1 was assigned based on nuclear Overhauser enhancement studies, which revealed an interaction between the methine protons on carbons 3a and 5. Yield: 5.65 g, 22.8 mmol, 80%. LCMS m/z 248.1 (M+1). 1H NMR (400 MHz, CDCl3) δ 1.51-1.63 (m, 1H), 2.17-2.24 (m, 1H), 3.40-3.52 (m, 1H), 3.49 (dd, half of ABX pattern, J=10.2, 4.2 Hz, 1H), 3.57 (dd, half of ABX pattern, J=10.2, 5.8 Hz, 1H), 3.68-3.77 (m, 1H), 3.79 (dd, J=11.8, 8.1 Hz, 1H), 4.23 (dd, J=13.5, 1.2 Hz, 1H), 4.54-4.65 (m, 3H), 4.77 (d, J=13.5 Hz, 1H), 7.27-7.39 (m, 5H).

Provenance & Evidence