Trifluoroacetic acid → (2R, 3S, 5S)-6-oxo-2,3-diphenyl-5-(3-tert-butyl-4-hydroxybenzyl)morpholine

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Reaction Steps

To a 250 mL 3-necked flask equipped with a nitrogen inlet and a magnetic stirrer were added 4.51 g of tert-butyl (2R, 3S, 5S)-6-oxo-2,3-diphenyl-5-(3-tert-butyl-4-((tert-butyldimethylsilyl)oxy)benzyl)-4-morpholinecarboxylate and 50 mL of anhydrous THF. The solution was cooled in an ice water bath, treated with 7.51 mL of 1M nBu4NF/THF (Aldrich), and then allowed to warm to RT with stirring under nitrogen. After 1.5 h, tlc (SiO2, 85:15 hexane:EtOAc) indicated no remaining starting material and a single new component at Rf =0.52. The solution was diluted with 125 mL of EtOAc, washed with water (4×100 mL), dried over MgSO4, and concentrated to give a thick, clear oil. Mass spectral analysis (APCI) indicated the desired intermediate with m/e=538 (M+H+Na)+. The oil was dissolved in 50 mL of CH2Cl2 and the solution treated with 15 mL of TFA. After stirring for 40 min, tlc (SiO2, 65:35 hexane:EtOAc) indicated a single new component at Rf =0.36. The solution was neutralized by addition of saturated aqueous NaHCO3. The mixture was transferred to a separatory funnel and the layers separated. The CH2Cl2 solution was washed with additional saturated NaHCO3 (3×50 mL), dried over MgSO4 and concentrated in vacuo to give a clear foam. The crude product was purified by flash chromatography (SiO2, 7:3 hexane:EtOAc) to afford 2.66 g (89%) of (2R, 3S, 5S)-6-oxo-2,3-diphenyl-5-(3-tert-butyl-4-hydroxybenzyl)morpholine as a white foam, m.p. 76-80° C.

Provenance & Evidence