(Cyanomethyl)triphenylphosphonium chloride → 3-[4-(2,6-Dioxo-1,3-dipropyl-2,3,6,7-tetrahydro-1H-purin-8-yl)-bicyclo[2.2.2]oct-1-yl]-acrylonitrile

Temperature

55 °C

To a stirred suspension of 4-(2,6-dioxo-1,3-dipropyl-2,3,6,7-tetrahydro-1H-purin-8-yl)-bicyclo[2.2.2]octane-1-carbaldehyde (535 mg, 1.44 mmol) and (cyanomethyl)triphenylphosphonium chloride (1.2 eq, 1.73 mmol, 582 mg) in THF (30 ml) at 0° C. was added KHMDS (0.5 M in toluene, 2.2 eq, 3.16 mmol, 6.3 ml). The resulting mixture was stirred for 1.5 h at this temperature then heated at 55° C. for 5 h. The cool reaction mixture was partitioned between EtOAc (10 ml) and a saturated aqueous NH4Cl solution (20 ml) and the aqueous phase was extracted with EtOAc (20 ml). The combined organic phases were washed with a saturated aqueous NaCl solution (2×20 ml), dried (MgSO4), filtered and evaporated to give a solid residue that was purified by radial chromatography (2 mm plate) using 5% MeOH in CH2Cl2 as eluent to afford 425 mg (75%) of a brittle foam (mixture of cis/trans isomers). MS: 396 (MH+).

1. customThe cool reaction mixture
2. customwas partitioned between EtOAc (10 ml)
3. extractiona saturated aqueous NH4Cl solution (20 ml) and the aqueous phase was extracted with EtOAc (20 ml)
4. washThe combined organic phases were washed with a saturated aqueous NaCl solution (2×20 ml)
5. dry with materialdried (MgSO4)
6. filtrationfiltered
7. customevaporated
8. customto give a solid residue that
9. customwas purified by radial chromatography (2 mm plate)
10. customto afford
11. addition425 mg (75%) of a brittle foam (mixture of cis/trans isomers)

ORD record

ord-972ce89f9b504b4cb74a556716c60f44

Source dataset

uspto-grants-2003_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06649600B1