Methyl iodide → tert-Butyl ((S)-1-azido-3-((R)-tetrahydro-2H-pyran-3-yl)propan-2-yl)(methyl)carbamate

Temperature

0 °C

To a solution of tert-butyl (S)-1-azido-3-((R)-tetrahydro-2H-pyran-3-yl)propan-2-ylcarbamate (30 mg, 0.11 mmol) in anhydrous THF (4 mL) at −78° C. was added 1.0 M LHMDS solution in THF (253 μL, 0.25 mmol), then stirred at this temperature for 30 min. To this mixture was added MeI (125 μL, 0.22 mmol), then the temperature was allowed to warm to 0° C., and stand for 12 hr in the refrigerator. The reaction mixture was quenched with saturated aq. NH4Cl, extracted with EtOAc (30 mL), the separated organic phase was washed with H2O (2×10 mL), brine, and dried (Na2SO4), and filtered. The filtrate was concentrated, the resulting slurry was purified through flash chromatography on silica gel (eluted with gradient system, 0-30% EtOAc in hexane) to afford tert-butyl (S)-1-azido-3-((R)-tetrahydro-2H-pyran-3-yl)propan-2-yl(methyl)carbamate 31 mg, yield 100%. MS ESI+ve m/z 321 (M+Na).

1. waitstand for 12 hr in the refrigerator
2. customThe reaction mixture was quenched with saturated aq. NH4Cl
3. extractionextracted with EtOAc (30 mL)
4. washthe separated organic phase was washed with H2O (2×10 mL), brine
5. dry with materialdried (Na2SO4)
6. filtrationfiltered
7. concentrationThe filtrate was concentrated
8. customthe resulting slurry was purified through flash chromatography on silica gel (eluted with gradient system, 0-30% EtOAc in hexane)

ORD record

ord-5a6ddb41d4e045109db116a77ed458bf

Source dataset

uspto-grants-2012_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08198453B2