Methoxymethyl-triphenylphosphonium chloride → HCID 178456482, compound

To a stirred suspension of methoxymethyl triphenylphosphonium chloride (1.1 g, 3.2 mmol) in THF (60 ml) at −78° C. was added a solution of KHMDS (0.5 M in toluene, 10 ml, 5 mmol). The resulting yellow mixture was stirred at this temperature for 1.5 h and a solution of 4-(2,6-dioxo-1,3-dipropyl-2,3,6,9-tetrahydro-1H-purin-8-yl)-bicyclo[2.2.2]octane-1-carbaldehyde (372 mg, 1.0 mmol) in THF (12 ml) was added over a period of 20 minutes. The mixture was held at −78° C. for 6 h and allowed to reach ambient temperature overnight (12 h). The reaction mixture was partitioned between saturated aqeuous NH4Cl (100 ml) and EtOAc (100 ml) and the aqueous phase was extracted with EtOAc (50 ml). The combined organic extracts were washed with saturated aqeuous NaCl (100 ml), concentrated in vacuo, redissolved in THF and concentrated to a volume of approx. 20 ml. To the solution was added an equal volume of 1 N HCl and the mixture was stirred overnight. The mixture was diluted with EtOAc (20 ml), the aqueous phase was separated and extracted with EtOAc (10 ml). The combined organic phases were then washed with saturated aqeuous NaCI (2×, 25 ml), dried (MgSO4), filtered and concentrated in vacuo. The resulting orange oil was purified in batches by radial chromatography (2 mm plate) using 3% MeOH and 3% THF in CH2Cl2 as eluent. Product-containing fractions were combined and concentrated to afford 290 mg (75%) of a white solid. MS: 387 (MH+).

1. waitThe mixture was held at −78° C. for 6 h
2. waitto reach ambient temperature overnight
3. custom(12 h)
4. customThe reaction mixture was partitioned between saturated aqeuous NH4Cl (100 ml) and EtOAc (100 ml)
5. extractionthe aqueous phase was extracted with EtOAc (50 ml)
6. washThe combined organic extracts were washed with saturated aqeuous NaCl (100 ml)
7. concentrationconcentrated in vacuo
8. dissolutionredissolved in THF
9. concentrationconcentrated to a volume of approx. 20 ml
10. additionTo the solution was added an equal volume of 1 N HCl
11. stirringthe mixture was stirred overnight
12. additionThe mixture was diluted with EtOAc (20 ml)
13. customthe aqueous phase was separated
14. extractionextracted with EtOAc (10 ml)
15. washThe combined organic phases were then washed with saturated aqeuous NaCI (2×, 25 ml)
16. dry with materialdried (MgSO4)
17. filtrationfiltered
18. concentrationconcentrated in vacuo
19. customThe resulting orange oil was purified in batches by radial chromatography (2 mm plate)
20. concentrationconcentrated

ORD record

ord-200e77c581e940538eb6138e34ee83b2

Source dataset

uspto-grants-2003_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06649600B1