Triphenylphosphine → 3-Methoxy-4-[(3R)-pyrrolidin-3-yloxy]benzonitrile

4-Hydroxy-3-methoxybenzonitrile (12 g, 80.2 mmol) and triphenylphosphine (21 g, 80.2 mmol) were added portionwise to an ice-cold solution of tert-butyl (3S)-3-hydroxypyrrolidine-1-carboxylate (15 g, 80.2 mmol) in tetrahydrofuran (225 mL). A solution of diisopropyl azodicarboxylate (16.2 g, 80.2 mmol) in tetrahydrofuran (100 mL) was then added dropwise and the mixture was stirred at room temperature for 18 hours. The reaction mixture was then concentrated in vacuo and the residue was treated with hydrochloric acid (4M in dioxane, 250 mL). The mixture was concentrated in vacuo and the residue was partitioned between ethyl acetate and water. The organic layer was separated and washed with water (100 mL), and the combined aqueous solution was washed with ethyl acetate (2×150 mL), basified to pH10 with solid potassium carbonate and extracted with ethyl acetate (2×250 mL). The combined organic solution was washed with brine (100 mL), dried over magnesium sulfate and concentrated in vacuo to afford the title compound as a cream solid in 67% yield, 11.8 g. LRMS ESI m/z 219 [M+H]+

1. concentrationThe reaction mixture was then concentrated in vacuo
2. additionthe residue was treated with hydrochloric acid (4M in dioxane, 250 mL)
3. concentrationThe mixture was concentrated in vacuo
4. customthe residue was partitioned between ethyl acetate and water
5. customThe organic layer was separated
6. washwashed with water (100 mL)
7. washthe combined aqueous solution was washed with ethyl acetate (2×150 mL)
8. extractionextracted with ethyl acetate (2×250 mL)
9. washThe combined organic solution was washed with brine (100 mL)
10. dry with materialdried over magnesium sulfate
11. concentrationconcentrated in vacuo

ORD record

ord-920c73773b514576867716c4215409cb

Source dataset

uspto-grants-2009_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07557131B2