Triphenylphosphine → HCID 10139468, compound

A solution of triphenylphosphine (0.915 mmol) in 5 mL of dry THF was treated at 0° C. with diethylazodicarboxylate (0.915 mmol) and stirred for 20 min. A solution of (2S)-3-[4-(5-hydroxy-pent-1-ynyl)-phenyl]-2-methoxy-propionic acid ethyl ester (Example 21, Step A) (0.61 mmol) and 4-benzoylphenol (0.915 mmol) in 2 mL of dry THF was added, and the mixture was stirred at room temperature overnight. The mixture was concentrated under vacuum and purified by silica gel chromatography (silica gel, hexanes/ethyl acetate 10:1 to 3:1). Fractions with Rfs 0.48 and 0.45 (hexanes/ethyl acetate 2:1) corresponding to the coupled compound and starting phenol, respectively, were combined and concentrated. The mixture was dissolved in 5 mL of methanol and was treated with a mixture of 75 mg of mercury (II) oxide and 4% sulfuric acid in water. The solution was stirred at 55° C. for 3 hours, cooled to room temperature, diluted with saturated aqueous NaHCO3 (20 mL), and extracted with dichloromethane (4×20 mL). The combined organic layers were washed with brine (20 mL), dried (MgSO4), and concentrated. The residue was dissolved in 6 mL of methanol and 2 mL of 1N NaOH and stirred for 2 hours. The methanol was evaporated under vacuum, and the aqueous solution was diluted with brine (6 mL) and washed with diethyl ether (3×15 mL). The aqueous layer was acidified with 1N HCl (pH 1–2) and extracted with ethyl acetate (3×15 mL) then concentrated to give the title compound. 1H-NMR (CDCl3, 200.15 MHz): 7.91–7.72 (m, 5H), 7.56–7.32 (m, 6H), 6.92 (d, 2H, J=8.9), 4.12–4.03 (m, 3H), 3.42 (s, 3H), 3.19–3.05 (m, 4H), 1.95–1.92 (m, 4H).

1. stirringthe mixture was stirred at room temperature overnight
2. concentrationThe mixture was concentrated under vacuum
3. custompurified by silica gel chromatography (silica gel, hexanes/ethyl acetate 10:1 to 3:1)
4. concentrationconcentrated
5. dissolutionThe mixture was dissolved in 5 mL of methanol
6. additionwas treated with a mixture of 75 mg of mercury (II) oxide and 4% sulfuric acid in water
7. stirringThe solution was stirred at 55° C. for 3 hours
8. additiondiluted with saturated aqueous NaHCO3 (20 mL)
9. extractionextracted with dichloromethane (4×20 mL)
10. washThe combined organic layers were washed with brine (20 mL)
11. dry with materialdried (MgSO4)
12. concentrationconcentrated
13. dissolutionThe residue was dissolved in 6 mL of methanol
14. stirring2 mL of 1N NaOH and stirred for 2 hours
15. customThe methanol was evaporated under vacuum
16. additionthe aqueous solution was diluted with brine (6 mL)
17. washwashed with diethyl ether (3×15 mL)
18. extractionextracted with ethyl acetate (3×15 mL)
19. concentrationthen concentrated

ORD record

ord-5279a43d96ca4e4583ce836bd8997be6

Source dataset

uspto-grants-2007_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07192982B2