Cerium(III) chloride → (2S)-tert-butyl 2-((tert-butyldimethylsilyloxy)methyl)-5-hydroxy-4-(methoxymethyl)-5,6-dihydropyridine-1(2H)-carboxylate

Participants

Reaction Conditions

Reaction Steps

To a stirred solution of Intermediate 117 (7.3 g, 19.65 mmol) in DCM (180 mL) was added N1,N1,N8,N8-tetramethylnaphthalene-1,8-diamine (25.3 g, 117.89 mmol). Then it was cooled to 0° C. and trimethyloxonium tetrafluoroborate (8.72 g, 58.94 mmol) was added. The reaction was then stirred at rt for several hours until LCMS showed the starting material was all consumed. Then it was concentrated under reduced pressure. The residue was then taken up in 100 mL Et2O and filtered, washed with 100 mL Et2O. The organic layer was then washed with 10% citric acid, aq NaHCO3, brine, dried over MgSO4, filtered and concentrated. The residue was then taken up in MeOH (180 mL), cooled to 0° C. and cerium(III) chloride (7.32 g, 19.65 mmol) was then added to give a clear solution. Then NaBH4 (0.743 g, 19.65 mmol) was added as solid, and the mixture was stirred from 0° C. to rt for 1 hr. The reaction mixture was concentrated in vacuo. The white solid was redissolved in 200 mL Et2O and washed with 10% citric acid, NaHCO3, brine, dried over MgSO4, filtered and concentrated. The residue was purified by silica gel column (20-80% Hex/EA, 80 g) to afford the title compound (6.20 g, 81%) as a colorless oil (−3.8:1 mixture of 2 diastereomers).

Provenance & Evidence