HCID 178418255, compound → HCID 60036805, compound

Participants

Reaction Conditions

Reaction Steps

The silylated imine from the previous step, e.g. (2R)-3-methyl-N—[(E)-2-pyridinylmethylidene]-1-[(trimethylsilyl)oxy]-2-butanamine was dissolved in dry THF (500 ml) and the solution was cooled down to −78° C. A 1 M solution of phenylmagnesiumbromide in THF (200 ml, 200 mmol, 2 eq) was added dropwise while the mixture was stirred by a magnetic bar. The mixture was further stirred 2 hours at −78° C. The temperature was then slowly increased up to room temperature overnight. A sample of the reaction mixture was quenched with aqueous NaHCO3 and analysed by LC-MS to detect the O-silylated products. After one night, the mixture was quenched with HCl 1M (250 ml) and the mixture was stirred at room temperature until the desilylation was complete (after 1 h, LC/MS analysis). The aqueous phase was further acidified with the addition of 5M HCl solution (20 ml). The aqueous phase was washed with 300 ml cyclohexane/Et2O (2:1), then made basic with 60 ml NaOH 5M at 0° C., and the organic products were extracted with Et2O, dried (MgSO4) and concentrated to give the desired product (XX*), e.g. (2R)-3-methyl-2-{[(R)-phenyl(2-pyridinyl)methyl]amino}-1-butanol as a yellowish oil (22.9 g, 85% yield, d.e.=99%, determined by 1H NMR).

Provenance & Evidence