Triethylamine → rel-(3aR,5R)-5-cyclopropyl-3,3a,4,5-tetrahydro-7H-pyrano[3,4-c][1,2]oxazole

Participants

Reaction Steps

An aqueous solution of sodium hypochlorite (6.15% solution, 27.1 mL, 22.4 mmol) was added drop-wise over 24 minutes to a solution of 2-[(1-cyclopropylbut-3-en-1-yl)oxy]-N-hydroxyethanimine (C17) (1.85 g, 10.9 mmol) and triethylamine (0.114 mL, 0.818 mmol) in dichloromethane (64 mL) that was immersed in a room temperature water bath. The rate of addition was adjusted to maintain the internal temperature of the reaction between 19.5° C. and 22.8° C. After completion of the addition, the reaction mixture was diluted with water (50 mL) and the aqueous layer was extracted with dichloromethane (3×50 mL). The combined organic layers were washed with saturated aqueous sodium chloride solution (50 mL), dried over sodium sulfate, filtered, and concentrated in vacuo (300 mbar, 40° C.) to provide the product as a pale yellow oil. The indicated relative stereochemistry of compound C18 was assigned based on nuclear Overhauser enhancement studies, which revealed an interaction between the methine protons on carbons 3a and 5. Yield: 1.73 g, 10.3 mmol, 94%. GCMS m/z 167 [M+]. 1H NMR (400 MHz, CDCl3) δ 4.73 (d, J=13.5 Hz, 1H), 4.61 (dd, J=10.2, 8.0 Hz, 1H), 4.14 (dd, J=13.5, 1.0 Hz, 1H), 3.80 (dd, J=11.5, 8.0 Hz, 1H), 3.36-3.48 (m, 1H), 2.83 (ddd, J=11.0, 8.0, 1.8 Hz, 1H), 2.31 (ddd, J=13.0, 6.5, 1.5 Hz, 1H), 1.64 (ddd, J=12.8, 11.4, 11.3 Hz, 1H), 0.89-0.98 (m, 1H), 0.51-0.64 (m, 2H), 0.38-0.45 (m, 1H), 0.21-0.28 (m, 1H).

Provenance & Evidence