Methoxymethyl-triphenylphosphonium chloride → Benzyl ((2R,3S)-1-(2,4-dimethoxybenzyl)-2-((E)-2-methoxyvinyl)-4-oxoazetidin-3-yl)carbamate

To a suspension of (methoxymethyl)triphenylphosphonium chloride (10.34 g, 30.2 mmol) in THF (100 mL) at −78° C. was added KHMDS (in toluene) (66.3 ml, 33.1 mmol) slowly. After stirring for 30 min, the above prepared ylide soln was added to a soln of benzyl ((2S,3S)-1-(2,4-dimethoxybenzyl)-2-formyl-4-oxoazetidin-3-yl)carbamate (3 g, 7.53 mmol) in THF (38 ml) at −78° C. After 3 h, the reaction mixture was quenched with saturated NaHCO3 (aq, 60 mL), and it was stirred overnight. The mixture was diluted with EtOAc, and the layers were separated. The aqueous layer was extracted with EtOAc (2×), and the combined organic layers were washed with brine, dried with Na2SO4 and concentrated in vacuo. The crude residue was purified via silica gel chromatography (EtOAc-Heptane, 0-60%) to afford the title compound (1.6 g, 49%) along with the trans-isomer (0.8 g, 25%). LCMS: Rt=0.91 min, m/z=427.0 (M+1). Method 2m_acidic.

1. waitAfter 3 h
2. customthe reaction mixture was quenched with saturated NaHCO3 (aq, 60 mL), and it
3. stirringwas stirred overnight
4. additionThe mixture was diluted with EtOAc
5. customthe layers were separated
6. extractionThe aqueous layer was extracted with EtOAc (2×)
7. washthe combined organic layers were washed with brine
8. dry with materialdried with Na2SO4
9. concentrationconcentrated in vacuo
10. customThe crude residue was purified via silica gel chromatography (EtOAc-Heptane, 0-60%)

ORD record

ord-e809db94b7cd4c1babcf29157b92b6c1

Source dataset

uspto-grants-2015_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09174978B2