Sodium Hydroxide → HCID 70279186, compound

Participants

Reaction Steps

N-butyllithium (1.70 mL, 2.5 M, 4.26 mmol) was added dropwise at 0° C. to a solution of acetone oxime (155.5 mg, 2.13 mmol)in anhydrous THF (10.0 mL). The resulting solution was stirred at the same temperature for two hours. trans-1-Methyl-4-(2,4,6-trimethylbenzoyloxy) proline methyl ester (21c, 500.0 mg, 1.64 mmol)in anhydrous THF (5.0 mL) was slowly added to the solution through syringe. The resulting mixture was further stirred at 0 ° C for eight hours and slowly warmed to room temperature overnight. THF was then evaporated in vacuo. A THF-sulfuric acid solution (10.0 mL, prepared in a ratio of sulfuric acid: THF: H2O=8.2 g: 40 mL: 10 mL) was added and the mixture was refluxed for two hours. The mixture was made basic with 10% NaOH and extracted with ethyl acetate (30 mL 4X). The combined organic extracts were washed with brine, dried over anhydrous magnesium sulfate and concentrated in vacuo. The resulting residue was purified by flash chromatography on silica gel eluting with ethyl acetate/hexane (1:1 and 2:1) to give 112.5 mg (21% yield) of the title compound (21 d) as an oil. TLC Rf =0.63 (ethyl acetate:hexane=2:l ). MS (DCl/NH3) m/e 329 (M+H)+. 1H NMR (CDCl3) δ: 6.86 (s, 2H, 2ArH), 6.03 (s, 1 H, isoxazole H), 5.48-5.54 (m, 1 H, OCH), 3.76 (dd, J =9.6, J=6.3 Hz, 1H, ArCHN), 2.38-2.61 (m, 4H, 2CH2), 2.44 (s, 3H, NCH3), 2.31 (s, 6H, 2ARCH3), 2.30 (s, isoxazole-CH3), 2.29 (s, 3H, ARCH3).

Provenance & Evidence